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These are the non-surgical facelift treatments to consider for glowing skin – VOGUE India

By daniellenierenberg

As eerily relevant as 1992s Death Becomes Her is in 2022, there is an unexpected difference. Unlike Madeline (Meryl Streep) and Helen (Goldie Hawn), we arent hiding our facelifts. Instead, some of us are live streaming the whole experience. Dermal fillers and Botox are getting as common as getting a facial in your local salon.

"There has been a shift of mindset and increased acceptability of these procedures, says Dr Madhuri Agarwal of Yavana Aesthetics, Mumbai. In the next few years, the trend is going to be more innovations and better delivery mechanisms of these minimally invasive procedures that deliver long term, healthy skin.

What you want to do to look and feel good is not up for discussion. While lasers and acids are wonderful for skin texture and even tightening, a non-surgical facelift involving needles can be more effective for the latter. For example, filler that is more natural looking, because a laser isnt doing anything to make up for the lost volume.

Our bodies are dynamic and need maintenance as we age. Even, and especially, our facial skin. But with so many options of non-surgical face lifts available, it can be overwhelming to make a choice. We spoke to a few dermatologists to help break down the details of the best non-surgical facelift treatments involving needles.

Botox involves injecting a very safe neurotoxin called Botulinum to freeze muscles, and relax them, ironing out wrinkles. Wary but curious first timers can choose to start with very minute unitsthey wont erase all wrinkles but will smoothen them out enough to look a little more natural. I suggest this only when fine lines form, says Dr Kiran Sethi, a dermatologist based in Delhi and author of Skin Sense. It lasts 3-6 months, and there isnt much downtime. Its great when combined with fillers or skin boosters. Theres also been a focus on preventive Botox. If you get it done before the lines set in, you will have fewer lines as you age, explains Dr Geetika Mittal Gupta of ISAAC Luxe Clinic in Mumbai and Delhi. You will need less and less Botox as you age, because those muscles are not contracting as much. And by early I mean, when you see certain lines of ageing.

Fillers are usually injections of hyaluronic acid that add back lost volume to parts of your face. The Indian bone structure is such that our cheekbone is a little flat on the centre part of the face, explains Dr. Chytra V Anand, founder, Kosmoderma located in Chennai and Bengaluru. So most Indians, even teenagers, get dark circles and hollows. Its a loss of volume. So you have to put a filler in there. And people are accepting of that. Its not because they want to look like someone else, or they want to look younger. They just want to maintain their body and skin. The down time for fillers is usually 2-7 days, depending on how easily you bruise. And a good treatment can last anywhere between 1 and 2 years.

The vampire facial might have shocked people a few years ago, but today its one of the most popular treatments in India. Platelet-rich plasma is extracted from your blood, rich in growth hormones that renews blood flow and tissue regeneration wherever it is injected back, including your scalp. Its usually a course of 3-4 sessions, monthly, says Dr Sethi. It treats melasma, dehydration, has a mild filler effect too. And when used on the scalp, new hair growth can show in 6 months.

Theres also stem cell therapy for hair and skin rejuvenation. We take a small biopsy of the skin, splice the cells, and use the extract for regenerative therapy, says Dr Anand. It takes less time and commitment than PRP and is great for scar healing.

Its good to remember that these treatments are addictive too, says Dr Akber Aimer, Director of Aesthetic Medicine, Maya Medi Spa. You need to understand your limit. Always look for a good doctor who is experienced and talk about your problems and ask their opinions. Understand everything clearly. Your decision-making is a multi-step procedure. You need to have done proper research on the materials used and the treatment. Understand the technology. Trust your gut. And dont forget to ask for before and after pictures!

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Japan’s five hottest biotech companies in healthcare – Labiotech.eu

By daniellenierenberg

While historically lacking in foreign investments, Japans biotech scene is thriving with global investors showing increasing interest. Here are five of the hottest Japanese private companies innovating in the healthcare space.

Japan boasts one of the highest life expectancies in the world, and, faced with a rapidly aging population, is witnessing a growing burden of chronic conditions including cardiovascular disease and type 2 diabetes. For this reason, the Japanese healthcare authorities are encouraging research into the treatment and prevention of these diseases, in addition to promoting the potential of regenerative medicine.

In addition to having a roster of healthcare giants including Takeda, Astellas Pharma and Eisai, Japan is also an Asian hotspot for biotech companies. Upcoming startups have historically been limited in foreign funding and reliant on local venture capital players such as Nippon Venture Capital, Shinsei Capital Partners, and the University of Tokyo Edge Capital Partners.

In 2021, however, the amount of foreign investment flowing into the Japanese biotech space rose to $98 million, almost triple the haul of previous years. The most prominent global backers included Newton Biocapital, F-Prime Capital, and SoftBank Group. This trend arose as the COVID-19 pandemic triggered a wave of investor enthusiasm in biotechnology around the world.

With the help of local experts, weve listed five of the hottest private biotech companies in Japan. These firms, shown in alphabetical order, have raised large funding rounds in the last two years and are developing innovative treatments for a range of conditions including cancer, cardiovascular disease and inflammatory disorders.

Source: Shutterstock

Founded: 2017

Headquarters: Fujisawa

Chordia Therapeutics derives its name from the English term chord referring to a collection of musical notes normally played in harmony. In a similar way, the company aims to work in harmony with stakeholders and collaborators to develop first-in-class small molecule treatments for cancer.

Chordias lead program is a drug that disrupts the processing of RNA in tumor cells. In a healthy cell, RNA molecules are typically transcribed from a DNA template and spliced together to guide the production of new proteins. Some cancer cells accumulate mutations in the RNA splicing machinery and become vulnerable to Chordias drugs that interfere with this process.

Chordia raised $31 million (4 billion yen) in a Series C round in May 2022. The aim of the round was to push the companys lead drug through phase I testing and fund the preclinical development of the rest of its pipeline.

This month, the company announced interim results from the phase I trial of its lead candidate, with four of the recruited patients so far showing signs of responding to the treatment.

Founded: 2015

Headquarters: Tokyo

Heart failure occurs when the heart muscle is irreparably damaged and is unable to pump blood. While this deadly condition can be treated with a heart transplant, there is a general shortage of donors available, making a pressing need for alternatives.

In June 2021, the stem cell therapy developer Heartseed raised $36.5 million (4 billion yen) in a Series C round. The mission is to provide a regenerative route to saving the heart via stem cell therapy.

In the lab, Heartseed reprograms skin cells from the patient into a type of stem cell called induced pluripotent stem cells and grows these stem cells into heart muscle cells. The company then injects the muscle cells as a small cluster, or seed, into heart tissue to repair the muscle.

The proceedings from its Series C round will allow Heartseed to take its lead candidate into clinical development, including a phase I/II trial scheduled for later this year. Last year, Heartseed also licensed its treatment to Novo Nordisk in Denmark to co-develop the treatment outside of Japan.

Founded: 2018

Headquarters: Tokyo

LUCA Science hit the headlines in the last week for raising an impressive $30.3 million (3.86 billion yen) in a Series B round. The company is developing an unusual approach for treating a wide range of diseases: delivering a therapy based on mitochondria, the energy production plants in human cells.

One example where the technology could work well is in strokes and heart attacks, where blood flow is blocked to critical tissue in the brain and heart respectively. The reperfusion of blood to these tissues after the blockage can kill the tissue by damaging its mitochondria. Delivering healthy mitochondria could keep the tissue working properly and protect it from harm.

LUCA Science plans to use its recent Series B winnings to accelerate the preclinical development of its mitochondrial therapies and establish its manufacturing process. In May 2022, the firm also inked a collaboration deal with compatriot pharmaceutical company Kyowa Kirin Co., Ltd. to co-develop a mitochondrial therapy for rare genetic diseases.

Founded: 2016

Headquarters: Boston, U.S., and Tokyo

Modulus Discovery is a preclinical-stage drug discovery specialist. The company focuses on developing small molecule treatments for conditions such as cancer, inflammatory disorders and rare genetic conditions.

The firm uses a mixture of strategies to speed up the drug discovery process. These include simulating target proteins using a supercomputer; structural protein biology; forming collaborations such as with the peptide drug expert PeptiDream; and tapping into global networks for biological expertise. Modulus most advanced drug program is in late-stage preclinical testing for the treatment of chronic inflammatory diseases.

In March 2022, Modulus bagged $20.4 million (2.34 billion yen) in a Series C round. The cash is earmarked to advance the companys R&D programs by expanding its infrastructure, collaborations and headcount.

Founded: 2015

Headquarters: Tokyo

The name Noile-Immune is derived from blending together the phrases no illness and no immunity, no life. This company is developing CAR-T cell therapies for the treatment of cancer, which traditionally consist of extracting the patients immune T cells, engineering them in the lab to hunt down cancer cells, and reinfusing them into the patient.

Unlike approved CAR-T cell therapies, which are limited to treating forms of blood cancer, Noile-Immune aims its therapies at treating solid tumors. The company does this by engineering immune T cells to produce proteins that cause immune cells to migrate into the tumor site.

Noile-Immune is testing its lead candidate in a phase I in patients with solid tumors. The firm is also co-developing therapies with partners including Takeda and the European cell therapy specialists Adaptimmune and Autolus. Additionally, Noile-Immune has an allogeneic version of its cell therapy in the pipeline where immune T cells are sourced from healthy donors rather than the patient.

To finance the clinical development of its lead candidate, Noile-Immune raised $21.8 million (2.38 billion yen) in a Series C round in early 2021. The company hit a setback in January 2022 when a collaboration deal fell through with the U.S. player Legend Biotech. Nonetheless, other external companies remain interested in Noile-Immunes offering, including Japan-based Daiichi Sankyo Company Ltd., which opted to assess Noile-Immunes technology in late 2021.

Cover image via Elena Resko.

Thanks to feedback from Shiohara Azusa, VC Investor at The University of Tokyo Edge Capital, and Hironoshin Nomura, Chief Financial Officer, Sosei Group Corporation.

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10 Years of Immunotherapy: Advances, Innovations, and Better Patient Outcomes – Targeted Oncology

By daniellenierenberg

The last decade of immunotherapy progress was based on decades of prior research, including other forms of immunotherapy.

Until recent years, cancer treatment revolved around surgery, chemotherapy, and radiation. But the FDA approval of ipilimumab (Yervoy) in 2011 led to a fourth leg of that treatment stool: immunotherapy. This enabled new treatment paradigms, sometimes with shocking levels of success.

The types of immunotherapy treatments available are proliferating, with approved immune checkpoint inhibitors (ICIs) and cellular therapies like chimeric antigen receptor (CAR) T cells as well as other modalities in the research and discovery phases. Some even include more established approaches like vaccines that are being revisited with new information and iterations.

The last decade of immunotherapy progress was based on decades of prior research, including other forms of immunotherapy. The Bacillus Calmette-Gurin vaccine, used to prevent tuberculosis for a century, has also been used as an immunotherapy to treat nonmuscle invasive bladder cancer since 1990.1 And rituximab (Rituxan), a monoclonal antibody therapy approved in 1997 for B-cell malignancies, is seen by some as an early immunotherapy as well.2

What many clinicians think of in terms of immunotherapy, however, are treatments targeting CTLA-4 and PD-1/PD-L1 pathways, brought from the bench by James P. Allison, PhD, and Tasuku Honjo, PhD, respectively, leading to a Nobel Prize awarded jointly to them in 2018.3

Immune responses are tightly controlled by T cells, and these T cells have on/off switches that help control their responses, according to Padmanee Sharma, MD, PhD, a professor in the Department of Genitourinary Medical Oncology in the Division of Cancer Medicine and the scientific director of the James P. Allison Institute at The University of Texas MD Anderson Cancer Center in Houston. Previously, she said, clinicians were not aware of the off switches. Sharma showed that CTLA-4 was an inhibitory pathway and that by blocking it, the T cells could stay longer to eradicate the tumors.

With 8 ICIs approved for immunotherapy in hematological and solid tumors,4 researchers are not only investigating newer forms of therapy, but also combining them to fi nd more effective and durable treatments and introducing them into earlier lines of treatment (TIMELINE). Current research is also attempting to predict who will respond to which therapy based on current and emerging biomarkers.

Ipilimumab, which kicked off the current era of cancer immunotherapy treatment with FDA approval in 2011, targets CTLA-4 for newly diagnosed or previously treated unresectable or metastatic melanoma.5 Ipilimumab blocks CTLA-4, removing its inhibitory signals. This allows the T cells to activate and launch an immune response to the tumors antigens.

CTLA-4 is basically the fi rst inhibitory pathway that comes up on the T cells, Sharma said. CTLA-4 is a member of an immunoglobulin-related receptor family responsible for some immune regulation aspects of T cells.6 It is thought to regulate T-cell proliferation mostly in lymph nodes, early in an immune response, by having an inhibitory role.7

What ipilimumab really did and what the immune checkpoint inhibitors really did is they opened up this whole different way to approach the immune system, Elizabeth Buchbinder, MD, a medical oncologist at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School in Boston, Massachusetts, said. Ipilimumab provided amazing durable responses in patients with melanoma with widely metastatic disease, some of whom were alive 10 years later, she said.

The PD-1 and PD-L1 blockades build on ipilimumabs success. Like CTLA-4, PD-1 is a negative regulator of T-cell immune function, inhibiting the target to increase immune system activation. PD-1 suppresses T cells mostly in the peripheral tissues.7 As of November 2021, 8 ICIs have been approved that target CTLA-4, PD-1, and PD-L1 pathways and treat 18 types of cancer.3

AntiPD-1 inhibitors

The percentage of people who benefi tted from ipilimumab was on the low side, Buchbinder said, with only an 11% response rate and 20% of people doing well long term in clinical trials. With PD-1 inhibition, however, there was approximately a 40% response rate and many more patients doing well long term, as demonstrated in clinical trials. So [PD-1 inhibition is] both far more effective and also less toxic, Buchbinder said.

When choosing an agent in the PD-1 class, we dont need to differentiate them. Theyre all antiPD-1, Sharma explained. There arent any data to indicate that patients will respond any differently to pembrolizumab [Keytruda] vs nivolumab [Opdivo]. The mechanism of action for both drugs [is] exactly the same.

Instead, clinicians should consider the FDA approvals for each drugs indications and combinations. But from a scientific standpoint, theres no distinguishing between [them], Sharma said.

AntiPD-L1 inhibitors

PD-1 and PD-L1 targeting drugs were found to work beyond melanoma and kidney cancer, the early indications for treatments targeting the CTLA-4 pathway, Buchbinder said. That was a huge opening up of this fi eld to all of these other cancers, like lung cancer, head and neck cancer, GI [gastrointestinal] cancer, breast [cancer], and beyond, she said.

Before receiving these immunotherapies, patients may need to show PD-1 or PD-L1 expression, although this may not identify all patients who can benefi t from the treatments. Researchers continue to try to identify additional and better biomarkers to indicate which patients may respond.13

In March, the FDA approved the newest ICI, nivolumab and relatlimab-rmbw (Opdualag), for adult and pediatric patients (12 years and older) with unresectable or metastatic melanoma. 3 Nivolumab is a PD-1 inhibitor, and relatlimab blocks LAG3 proteins on immune cells. It is being tested in a lot of other tumors, Buchbinder noted.

Another target in the discovery phase is T cell immunoglobulin and mucin domain 3, which is a checkpoint receptor expressed by many immune cells and leukemic stem cells.14 It is activated by several ligands and is being tested in different cancer types.

Also in clinical trials are tumor-infiltrating lymphocytes (TIL) that recognize cancer cells as abnormal, entering the tumor to kill the cells. TILs already recognize the targets because they originate from the tumor itself.15 Although they need to be expanded, they are not the same as CAR T cells, which must be engineered to recognize the targets.

In addition, older therapies are experiencing a resurgence, with research underway to make interleukin 2 (IL-2) help cytokines function better. That work is trying to optimize what those cytokines do in the body and the immune system, Buchbinder said. There are so many areas where the goal of the therapy is activation of the immune system.

One of these areas includes a return to vaccines. In earlier vaccine therapy, We had no idea that while we were giving therapy to turn on the cells, we were also rapidly turning off the cells because an on switch will automatically drive an off switch for the immune system, Sharma said. The yin and the yang of the immune response is very important to understand because when the immune response is driven in one direction, it will always try to control itself. With that in mind, newer vaccines might work better if given in combination with an antiCTLA-4, for example, to block the inhibitory pathways, she said.

Vaccines are taking many forms, including the mRNA vaccine used for COVID-19, peptide vaccines that include a tiny bit of protein that is expected to be expressed on the tumor surface, and vaccines constructed from dendritic cells, which stimulate T cells, Buchbinder said.

There are also viral therapies injected directly into tumor vaccines, such as talimogene laherparepvec (Imlygic) approved in 2015 for the treatment of some patients with metastatic melanoma that cannot be surgically removed.16 It is a is a modifi ed herpes virus directly injected into the tumor to bring about a local immune response, Buchbinder said.

According to Sharma, approximately 60 targets are currently being evaluated for immunotherapy development.

The FDA has approved 2 CAR T-cell therapies, both in 2017: tisagenlecleucel (Kymriah) for patients 25 years and younger with relapsed B-cell precursor acute lymphoblastic leukemia17 and axicabtagene ciloleucel (Yescarta) for the treatment of adult patients with large B-cell lymphoma that is refractory to fi rst-line chemoimmunotherapy or that relapses within 12 months of fi rst-line chemoimmunotherapy.18 These treatments involve collecting T cells from the patient and engineering them to express CARs that recognize the patients cancer cells. The cells are then enlarged and infused back into the patient, where they can target the antigen- expressing cancer cells. CARs have been shown to greatly improve clinical response and disease remission in some patients.19

I think CAR T cells are clearly building on the concept that T cells are the soldiers of immune response. They are basically engineering the cell to have an antibody that recognizes a specifi c antigen, Sharma said, adding that its important to ensure the targeted antigen is part of the cancer.

CAR T cells have had limited effectiveness in treating solid tumors, given the low T-cell infiltration and immunosuppressive environment that challenges the immune system from successfully reaching and killing solid tumor cancer cells.20

Natural killer (NK) cells are another cell type being researched to attempt tumor eradication, and this therapy is in the early stages, according to Sharma. CAR NK cells can be generated from allogenic donors, making them more attractive as off the shelf treatments compared with CAR T cells, which are collected from the patient. As of early 2021, more than 500 CAR T-cell trials and 17 CAR T-cell/NK-cell trials were in the works globally.21

A major consideration when choosing any treatment, including immunotherapies, is the adverse event (AE) profile. Immunotherapy drugs have different AEs than oncology treatments like chemotherapy or radiation. [With immunotherapy,] what we see is infl ammation because youre turning on the immune system in such a powerful way, Sharma said. Inflammatory reactions include a skin rash or dermatitis, infl ammation in the colon (colitis and diarrhea), and/or infl ammation in the lung with pneumonitis. Clinicians are now aware of these AEs and can monitor them closely, stopping therapy if needed to control them before they become severe, Sharma said.

Toxicities with ipilimumab can be severe, and patients requiring hospital admission might need high-dose steroids, Buchbinder noted. Common AEs for the CTLA-4 inhibitor are typically GI related, including diarrhea, colitis, and hepatitis. Some patients may experience fatigue or a small rash, but most generally make it through treatment with minimal AEs.

The stronger AEs with ipilimumab can be seen from a trial comparing ipilimumab plus nivolumab to nivolumab and relatlimab. Almost 60% of patients experienced AEs with the ipilimumab combination vs 20% in the latter group.17

PD-1 and PD-L1 inhibition typically involve AEs that cause lung issues rather than GI. The types of organ systems affected by immunotherapy AEs can vary based upon which checkpoint inhibitor you use but in some ways, the mechanism by which these occur is very similar, Buchbinder said. Its all an overactivation of the immune system leading to infl ammation in an organ, and there are very few organs that we have not seen toxicity from immunotherapy.

Buchbinder noted that cellular therapies can cause more severe AEs, such as cytokine release syndrome (CRS). Patients can get very sick very quickly, she said, because the therapies given with the cellsincluding the chemotherapy given before and the IL-2 given aftercause most of the AEs. With a lot of the injection therapies, the AEs are related to delivery method, like injection-site issues, but there are also potential systemic AEs like fever, chills, and reactions someone would get to a virus. Its really a huge range in terms of the different [adverse] effects, Buchbinder said.

CRS is the most common AE of CAR T-cell therapy, and it is caused by large numbers of T cells activating, which releases inflammatory cytokines. Although this demonstrates that the therapy is working, it can cause worrisome symptoms. The CRS and the related neurotoxicity can be treated with tocilizumab (Actemra).

One question in the immunotherapy world is whether the development of immune-related AEs predicts a positive or negative response to treatment. With melanoma, we think the data have been very tricky, Buchbinder said. Early trials appeared to show a higher response rate for patients who developed severe symptoms, but as trials developed, that signal was not always there. I think the overall impression is that yes, severe AEs are associated with a better response, she said. A cosmetic AE that clinicians who treat melanoma are excited to see, she said, is vitiligo. It suggests that the immune system is attacking normal melanocytes and that it is attacking cancer cells as well. Those patients generally do far better than patients who dont get vitiligo.

A meta-analysis of 30 studies on the topic, including 4971 individuals, showed that patients who developed immune-related AEs experienced an overall survival benefi t and a progression-free survival benefi t using ICI therapy compared with those who did not. The authors stated that more studies are needed and that the results are controversial.22

Melanoma has been the proving ground for ICIs, Buchbinder said, But now the bar is higher in terms of immunotherapy.

ICIs are now being tested in more immuneresistant tumors. Although there are huge hurdles in terms of some cancers where its going to be hard for immune therapy to do muchlike pancreatic cancer or prostate cancerthere are still diseases where theres opportunity and a possibility that the correct approach or combination might get to some great therapy for those diseases, Buchbinder said

Immunotherapies are being combined with conventional therapies to better integrate treatment. We dont see cancer as a death sentence anymore, Sharma said. We really do see a lot of hope, [and patients with cancer] should be encouraged to discuss immunotherapy with their physician either in a clinical trial or an FDA-approved agent. If you do have a response, its a pretty phenomenal response.

REFERENCES:

1. Lobo N, Brooks NA, Zlotta AR, et al. 100 years of Bacillus Calmette- Gurin immunotherapy: from cattle to COVID-19. Nat Rev Urol. 2021;18(10):611-622. doi:10.1038/s41585-021-00481-1

2. Pierpont TM, Limper CB, Richards KL. Past, present, and future of rituximab-the worlds fi rst oncology monoclonal antibody therapy. Front Oncol. 2018;8:163. doi:10.3389/fonc.2018.00163

3. Kruger S, Ilmer M, Kobold S, et al. Advances in cancer immunotherapy 2019 - latest trends. J Exp Clin Cancer Res. 2019;38(1):268. doi:10.1186/s13046-019-1266-0

4. Lee JB, Kim HR, Ha SJ. Immune checkpoint inhibitors in 10 years: contribution of basic research and clinical application in cancer immunotherapy. Immune Netw. 2022;22(1):e2. doi:10.4110/in.2022.22.e2

5. FDA approves Yervoy (ipilimumab) for the treatment of patients with newly diagnosed or previously-treated unresectable or metastatic melanoma, the deadliest form of skin cancer. News release. Bristol Myers Squibb. March 25, 2011. Accessed May 11, 2022. https://bit.ly/3PFp7q2

6. Rowshanravan B, Halliday N, Sansom DM. CTLA-4: a moving target in immunotherapy. Blood. 2018;131(1):58-67. doi:10.1182/ blood-2017-06-741033

7. Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39(1):98-106. doi:10.1097/COC.0000000000000239

8. Keown A. Keytruda approvals: a timeline. BioSpace. Aug 13, 2019. Accessed May 11, 2022. https://bit.ly/3yHvfrL

9. Stewart J. Opdivo FDA approval history. Drugs.com. Updated March 15, 2022. Accessed May 20, 2022. https://bit.ly/3lnmtar

10. Markham A, Duggan S. Cemiplimab: fi rst global approval. Drugs. 2018;78(17):1841-1846. doi:10.1007/s40265-018-1012-5

11. FDA grants accelerated approval to dostarlimab-gxly for dMMr endometrial cancer. FDA. Updated April 22, 2021. Accessed May 20, 2022. https://bit.ly/38BSJns

12. Pierpont TM, Limper CB, Richards KL. Past, present, and future of rituximab-the worlds first oncology monoclonal antibody therapy. Front Oncol. 2018;8:163. doi:10.3389/fonc.2018.00163

13. Opdualag becomes fi rst FDA-approved immunotherapy to target LAG-3. National Cancer Institute. April 6, 2022. Accessed May 11, 2022. https://bit.ly/3FZWaAp

14. Acharya N, Sabatos-Peyton C, Anderson AC. TIM-3 finds its place in the cancer immunotherapy landscape. J Immunother Cancer. 2020;8(1):e000911. doi:10.1136/jitc-2020-000911

15. Boldt C. TIL Therapy: 6 things to know. MD Anderson Cancer Center. April 15, 2021. Accessed May 11, 2022. https://bit.ly/3wmguJb

16. FDA approves talimogene laherparepvec to treat metastatic melanoma. National Cancer Institute. November 25, 2015. Accessed May 20, 2022. https://bit.ly/3woTDwA

17. OLeary MC, Lu X, Huang Y, et al. FDA approval summary: tisagenlecleucel for treatment of patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Clin Cancer Res. 2019;25(4):1142-1146. doi:10.1158/1078-0432.CCR-18-2035

18. FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. News release. FDA. Oct. 18, 2017. Accessed May 11, 2022. https://bit.ly/3wpECL1

19. FDA approves fi rst CAR T-cell therapy the evolution of CAR T-cell therapy. Cell Culture Dish. October 24, 2017. Accessed May 10, 2022. https:// bit.ly/3LlDD2B

20. Albinger N, Hartmann J, Ullrich E. Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany. Gene Ther. 2021;28:513-527. doi:10.1038/s41434-021-00246-w

21. Ahmad A, Uddin S, Steinhoff M. CAR-T cell therapies: an overview of clinical studies supporting their approved use against acute lymphoblastic leukemia and large B-cell lymphomas. Int J Mol Sci. 2020;21(11):3906. doi:10.3390/ijms21113906

22. Zhou X, Yao Z, Yang H, Liang N, Zhang X, Zhang F. Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? a systematic review and meta-analysis. BMC Med. 2020;18(1):87. doi:10.1186/s12916-020-01549-2

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10 Years of Immunotherapy: Advances, Innovations, and Better Patient Outcomes - Targeted Oncology

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Researchers develop living skin and graft it onto a robotic finger – ZME Science

By daniellenierenberg

Robotic innovations are accelerating at a startling rate, with the development of our humanoid counterparts taking sometimes hitting very close to the real thing. Consequently, the integration of these human-like robots into our society is a priority for many research groups across the globe. Now, a research team from Tokyo University has brought us even closer to this goal by growing human skin on a robotic skeleton to create a biohybrid robot.

The development of robots made to look like humans has sparked a fiery debate in research circles, prompting some to call for a clearer line between inanimate machines and autonomous robots. To illustrate this distinction, picture a ceiling fan whirling around at a constant speed when turned on manually this is an automated machine. But when we add a temperature sensor and a processor capable of storing user preferences and environmental data, the fan can then avoid obstructions and function autonomously based on the local temperature. The machine becomes an intelligent robot attuned to its environment a first step towards becoming more human.

At present, engineers are taking this premise even further, working on robots that have more and more in common with humans. If robots do become human-like, they could become widely used in any number of applications, but developing robots that feel like humans do isnt an easy feat.

The authors of a new study explain that blurring the line between humans and robots is one of the top priorities for humanoids tasked to interact with humans. But, presently, silicone skin used in robotics falls short when it comes to the delicate textures and expressions perceived by the human derma and underlying muscles. Additionally, synthetic skin cant heal, with patches or a silicone sealant used to repair rather than regenerate worn or torn areas.

To overcome this challenge, researchers have fashioned living skin sheets that can bond to the robots frames. However, conforming these biological coverings to the frameworks uneven surfaces and sharp, dynamic joints has proven extremely challenging. It got even worse when the humanoid moves the 3-dimensional (3D) metal chassis and joints damage the skin even further, causing gross failure.

So a new solution was needed. In the new study, the team cleared this hurdle using a novel technique that can grow living human skin onto a three-jointed robotic finger. The human-like skin consists of living cells and an extracellular matrix-a 3d support system holding cells in place-exhibiting self-healing properties while allowing the jointed structure underneath to move freely.

Our goal is to develop robots that are truly human-like, first author Professor Shoji Takeuchi, from the University of Tokyo, told ZME Science in an email. The silicone rubber covers that are commonly used today may look real from a distance or in photos or videos, but when you actually get up close, you realize that it is artificial. We think that the only way to achieve an appearance that can be mistaken for a human being is to cover it with the same material as a human being, i.e., living cells. Using cells would also allow the robot to work with the excellent biological functions of skin, such as its ability to self-repair.

To fashion the biohybrid robotic finger, the team first assembled the framework and coated it with parylene, a polymer used to protect implanted medical devices from moisture and contamination in the body. Similarly, the coating prevented any toxic materials in the robotic skeleton from leaching into the human skin equivalent and damaging it.

After this, they engineered a living dermis (the middle layer of skin responsible for protecting the human body from the outside world) that can feel different sensations and produce sweat. Once this was done, they then seeded the epidermis (the outermost layer of skin in the human body that protects against foreign substances and excessive water loss).

Expanding on this, the team explains that they placed the coated robotic finger in an outsized mold to engineer the dermis. Inside the mold, there was a solution of collagen and human dermal fibroblasts, the two main components that make up this connective tissue in the human body. To ensure the dermis was seeded correctly, the framework was cultured for 14 days, and an anchor was attached to the fingers base.

Takeuchi explains how the studys success hinges on this anchor because the collagen naturally shrinks, covering the robotic substructure tightly. Conversely, if there were no anchor at the base of the finger, the collagen would contract, retreating up the stem of the robotic digit. Like a primer, the dermis equivalent provided a uniform foundation for the next coat of cells (called keratinocytes) to form the epidermis.

This time, enough room was left in the mold to form a cap at the top of the structure to add extra tensile strength to the materials, enabling a uniform thickness of living skin across the frame. Results showed that this cap prevented damage to the human-like skin once the finger and joints were in motion.

One particular difficulty was culturing the skin to match its three-dimensional aspect. We found that we could adapt the skin to the curved 3D surface shape by culturing it on site, rather than making it elsewhere and attaching to the surface. By installing an appropriate anchor structure, the entire surface could be covered, Takeuchi told ZME Science.

This method can be used to cover the 3D surface of a robotic finger while controlling tissue shrinkage through anchor fixation. In addition, multidirectional seeding of keratinocytes enables us to uniformly form the epidermis layer, the team stated in their paper.

When testing the human-skin equivalent for tensile strength and water resistance, these layers produced a skin-like texture possessing moisture-retaining properties. Additionally, the biohybrid structure had enough strength and elasticity to allow curling and stretching movements and could handle electrostatically charged polystyrene foam packing balls when allocated a task.

The team also used a skin graft technique to evaluate their skins self-healing properties. To accomplish this, they cut a hole in the biohybrid fingers skin and applied a collagen bandage to the wound. Subsequently, this patch was integrated with the human-like skin to withstand continuous movement.

Despite these promising results, the group cautioned that their crafted skin is much weaker than human skin, and they dont expect this robot human-skin-equivalent to survive for very long. The team now plans to incorporate more biological structures into their skin to address these issues, such as sensory neurons, hair follicles, nails, and sweat glands.

Speaking to ZME Science about their results overall, Takeuchi concludes that It was exciting to find that a robotic finger, completely covered with skin, could stretch and contract when it moved, without breaking, and that it could repair itself by cell proliferation when damaged. We believe this is a great step toward a new biohybrid robot with the superior functions of living organisms.

The study is published in the journalMatter.

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Anemia and Diabetes: What You Should Know – Healthline

By daniellenierenberg

If you live with diabetes, you may be aware that having the condition and its complications may put you at greater risk of developing anemia. But how are the two conditions related and what does this mean for you?

This article will investigate the relationship between diabetes and anemia, and what you should know if you have diabetes-related complications impacting your life.

According to the National Heart, Lung, and Blood Institute, Anemia is a condition in which the blood doesnt have enough healthy red blood cells to function properly. This leads to reduced oxygen flow to the bodys organs.

There are more than 3 million cases of anemia diagnosed in the United States every year, making this a very common condition.

You may experience the following symptoms:

Its important to note that some anemia symptoms are similar to symptoms of high blood sugar, including dizziness, lightheadedness, extreme fatigue, rapid heart rate, and headache.

Check your blood sugar often to make sure youre not confusing high blood sugar for suspected anemia. If your symptoms continue for a few days or weeks without high blood sugar numbers or ketones, call a healthcare professional to get checked for anemia.

Diabetes doesnt cause anemia and anemia doesnt cause diabetes. The two conditions are related, though.

Up to 25 percent of Americans with type 2 diabetes also have anemia. So its relatively common for people with diabetes, and especially diabetes-related complications, to also develop anemia.

However, if you have one condition or the other, you wont automatically develop the other condition.

As seen in this 2004 study, Anemia is a common complication of people with diabetes who develop chronic kidney disease because damaged or failing kidneys dont produce a hormone called erythropoietin (EPO), which signals to the bone marrow that the body needs more red blood cells to function.

Early stages of kidney disease (nephropathy) may be asymptomatic, but if youre diagnosed with anemia and you have diabetes, it might be a sign that your kidneys arent working properly.

People with diabetes are also more likely to have inflamed blood vessels. This prevents the bone marrow from even receiving the EPO signal to create more red blood cells to begin with. That makes anemia a more likely result.

Additionally, if you have existing anemia and are then diagnosed with diabetes, it may make you more likely to develop diabetes-related complications, such as retinopathy and neuropathy (eye and nerve damage).

A lack of healthy red blood cells can additionally worsen kidney, heart, and artery health, systems that are already taxed with a life lived with diabetes.

Certain diabetes medications can decrease your levels of the protein hemoglobin, which is needed to carry oxygen through the blood. These diabetes medications can increase your risk of developing anemia:

Since blood loss is also a significant contributor to the development of anemia, if you have diabetes and are on kidney dialysis, you may want to talk with your healthcare team about your increased risk of anemia as well.

Anemia can affect blood sugar levels in several ways.

One 2010 study found that anemia produced false high blood sugar levels on glucose meters, leading to dangerous hypoglycemia events after people overtreat that false high blood sugar.

As shown in a 2014 study, theres a direct link between anemia caused by iron deficiency and higher amounts of glucose in the blood. A 2017 review of several studies found that in people both with and without diabetes, iron-deficiency anemia was correlated with increased A1C numbers.

This resulted from more glucose molecules sticking to fewer red blood cells. After iron-replacement therapy, HbA1c levels in the studies participants decreased.

If you receive an anemia diagnosis and you live with diabetes, there are many excellent treatment options.

Treatment will depend on the underlying cause of the condition, but may include supplementation with iron and/or vitamin B.

If your anemia is caused by blood loss, a blood transfusion may be necessary. If your bodys blood production is reduced, medications to improve blood formation may be prescribed.

Diabetes and anemia are closely related, though neither directly causes the other condition.

Diabetes-related complications such as kidney disease or failure and inflamed blood vessels may contribute to anemia. Certain diabetes medications can also increase the likelihood of developing anemia. Anemia may also make diabetes management more challenging, with higher A1C results, false high blood sugars, and a potential risk of worsening organ health leading to future diabetes complications.

Still, anemia is very treatable with supplementation, dietary or medication changes.

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The Many Spheres in Which CO2 Chambers Show Their Strengths – MedicalExpo e-Magazine

By daniellenierenberg

Without CO2 incubators, there would be no coronavirus vaccines today. They are also absolutely essential for cancer research. These multiple uses help save lives and cure many different diseases. We would now like to introduce you to some of the interesting facets of CO2 incubators.

Sponsored by BINDER GmbH.

CO2 incubators are being used to conduct research in laboratories across the globe. The Bioscience Institute Middle East, which is among the worlds leading centers for regenerative medicine, is also using an incubator to process the bodys own cells as well as for plastic surgery applications.

The cellswhich are multiplied in an incubatorare also used in tissue repair as well as for orthopedic and dermatological treatments. The Bioscience Institute only uses skin and fat tissue specimens from adult (mature) cells. Using the bodys owni.e., autologouscells eliminates the risk of rejection while also preventing the complication of graft-versus-host disease (an unwanted reaction of the donors immune cells).

To be even more specific: the CO2 incubators are predominantly used to incubate stem cells from mesenchyme tissue (undifferentiated connective tissue).

Here is how it works: first, cells are extracted from fat tissue. This process is performed by means of enzymatic disaggregation (separation) using various steps of filtration and centrifugation. The crucial stage here is the expansion, i.e., extracting as many stem cells as possible, which is why it is absolutely essential to create the best possible growth conditions.

Dr. Simona Alfano, a biologist at the Bioscience Institute, explained:

When incubating the cells, it is vitally important for the selected parameters to remain exactly constant across all levels.

And this is precisely where the CO2 chambers from BINDER come into their ownwith their reproducible growth conditions, constant climatic conditions, low risk of contamination and high level of safety.

Find out more about why the ph value is a key factor in cell and tissue cultures.

CO2 chambers also played an important role during the coronavirus pandemic: firstly, in the development of coronavirus vaccines and, secondly, to test drugs that may be used to treat COVID-19 on cells.

For this work, the major pharmaceutical companies required huge volumes of cellswhich they were able to acquire with the aid of an incubator. The newly developed active ingredients were then tested using the cells.

The new vaccines used in the fight against the coronavirus were also repeatedly tested on cells in laboratories and evaluated. An incubator proved to be an essential piece of equipment in a laboratoryparticularly during the coronavirus pandemic.

Read more on premium equipment for virus research.

The Institute of Medical Engineering at the Lucerne University of Applied Sciences and Arts has been carrying out research in the field of space biology. The research team, led by Dr. Fabian Ille, is assisted in its work by a CO2 chamber.

Cells from a bovine hoof are being incubated inside the cabinet at regular intervals until they are needed for a specific experiment. Recently, the cells were frozen and taken to the French city of Bordeaux by Dr. Simon West and a team of researchers.

The reason behind this trip was that the research team in Lucerne was selected by the European Space Agency (ESA) to take part in parabolic flights over the Atlantic. Shortly before the parabolic flights, which lasted for a total of three hours, the cells were removed from the incubator and moved to flight hardware that had been prepared specifically for this purpose and was under controlled temperature conditions.

The scientists from Lucerne wanted to use the parabolic flights to investigate how the cells respond and adapt to mechanical forces. These findings will help them in future attempts to cultivate cartilage that is of a stronger and better consistency, for example. In other words, it might be possible to remove cells from a patient, reproduce them with this innovative new method, and then use them again in the treatment of human patients.

Weightless conditions are helping us to make significant progress, said Dr. Ille, reflecting on the research project so far.

In laboratory tests that have already been carried out, West and Ille have been able to demonstrate in very broad terms that this process could work in the future.In these tests, weightless conditions were simulated using a random position machine. Here again, a CO2 chamber from BINDER was used.

Safety is the absolute top priority here.180C sterilization ensures, for example, that every trial series begins with a clean and fully sterile incubator. Whats more, the fanless design means that germs are not stirred up.

The result is optimal cell growth and absolutely no contamination from airborne germs. A deep-drawn inner chamber without corners or edges also enables the incubator to be cleaned thoroughly with ease. It is therefore no surprise that major pharmaceutical manufacturers choose specifically to put their trust in CO2 incubators from BINDER.

BINDER CO2 incubators are the perfect combination of a range of solutions180C hot air sterilization, rapid control, fixture-free interiors and absolutely zero consumables. For optimal cell growthsafe, reliable, smart, economicallook no further than BINDER.

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Pediatric Urologist Dr. Anthony Atala to Receive 2022 Jacobson Innovation Award of the American College of Surgeons for Pioneering Work in…

By daniellenierenberg

Newswise CHICAGO (June 10, 2022): Anthony Atala, MD, FACS, Winston-Salem, North Carolina, will be presented with the 2022 Jacobson Innovation Award of the American College of Surgeons (ACS) at a dinner held in his honor this evening in Chicago. He is currently the George Link, Jr. Professor and Director of the Wake Forest Institute for Regenerative Medicine (WFIRM) and the W. H. Boyce Professor and Chair of Urology at the Wake Forest University School of Medicine.

The international surgical award from the ACS honors living surgeons who are innovators of a new development or technique in any field of surgery. It is made possible through a gift from Julius H. Jacobson II, MD, FACS, and his wife Joan. Dr. Jacobson is a general vascular surgeon known for his pioneering work in the development of microsurgery.

Dr. Atala is a pediatric urologist, researcher, professor, and mentor who is renowned for developing foundational principles for regenerative medicine research, which holds great promise for people who require tissue substitution and reconstruction. Dr. Atala and his team successfully implanted the worlds first laboratory grown bladder in 1999.

Dr. Atalas remarkable work has expanded, and today, WFIRM is a leader in translating scientific discovery into regenerative medicine clinical therapies. He currently leads an interdisciplinary team of more than 450 researchers and physicians. Beyond many other world firsts, WFIRM has also developed 15 clinically used technology-based applications, including muscle, urethra, cartilage, reproductive tissues, and skin. Currently, the Institute is working on more than 40 tissues and organs.

Through Dr. Atala's vision, ingenuity, and leadership, the WFIRM team has developed specialized 3-D printers to engineer tissues. This work is accomplished by using cells to create various tissues and organs, including miniature organs called organoids to create body-on-a-chip systems. Dr. Atala and his team also discovered a stem cell population derived from both the amniotic fluid and the placenta, which are currently being used for clinically relevant research applications.

Dr. Atala's theory is that every cell within the human body should be capable of regeneration. What reproduces naturally inside the body should also have the same capabilities of reproduction outside of the body. According to Dr. Atala, the key benefit to the approach of cell and tissue regeneration is that a patient will not reject their own cells or tissue, which is always a concern related to traditional organ match transplantation.

Honors and awards Dr. Atalas innovative work has been recognized as one of Time magazine's Top 10 Medical Breakthroughs in 2007, Smithsonian's 2010 Top Science Story of the Year, and U.S. News & World Report's honor as one of 14 top Pioneers of Medical Progress in the 21st Century. He has been named by Scientific American as one of the world's most influential people in biotechnology, by Life Sciences Intellectual Property Review as one of 50 Key Influencers in the Life Sciences Intellectual Property arena, and by Nature Biotechnology as one of the top 10 Translational Researchers in the World.

Dr. Atala was elected to the Institute of Medicine of the National Academies of Sciences (now the National Academy of Medicine) in 2011 and inducted into the American Institute for Medical and Biological Engineering. In 2014, he was inducted into the National Academy of Inventors as a Charter Fellow and has been a strong and thoughtful contributor to the ACS Surgical Forum and Surgical Research Committee. He presented the prestigious Martin Memorial Named Lecture during the ACS Clinical Congress in 2010 entitled, Regenerative Medicine: New Approaches to Health Care.

Other honors include being the recipient of the U.S. Congress-funded Christopher Columbus Foundation Award, which is bestowed on a living American that currently is working on a discovery that will significantly affect society; the World Technology Award in Health and Medicine for achieving significant and lasting progress; the Edison Science/Medical Award; and the Smithsonian Ingenuity Award.

A national leader in regenerative medicine Throughout his distinguished career, Dr. Atala has led or served on several national professional and government committees, including the National Institutes of Health Working Group on Cells and Developmental Biology, the National Institutes of Health Bioengineering Consortium, and the National Cancer Institute's Advisory Board. He is a founder of the Tissue Engineering Society, the Regenerative Medicine Society, the Regenerative Medicine Foundation, the Alliance for Regenerative Medicine, the Regenerative Medicine Development Organization, the Regenerative Medicine Manufacturing Society, and the Regenerative Medicine Manufacturing Consortium.

A prolific author and inventorDr. Atala is the editor in chief of Stem Cells-Translational Medicine and BioPrinting. He is an author or coauthor of more than 800 journal articles and has applied for or received over 250 national and international patents.

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About Anthony Atala, MD, FACS

Dr. Atala was born in Lima, Peru, and moved to the United States with his family when he was a young boy. He earned a Bachelor of Arts degree from the University of Miami before attending medical school at the University of Louisville, where he also completed his surgical residency training. Near the end of his residency, he applied for a pediatric urology fellowship at Boston Children's Hospital, which was transitioning from a one-year to a two-year program to include a year of research prior to the clinical year. He embarked on a fellowship there in its new form with encouragement from Alan B. Retik, MD, FACS, founder of Boston Childrens first department of urology. Dr. Atala arrived in Boston and began attending seminars, which led him to explore whether uroepithelial cells could be grown and expanded ex vivo, comparable to skin. This additional year of research sparked what has become his career of transformational research, discovery, and innovation with his work focused on growing human cells, tissues, and organs.

Dr. Atala spent the first portion of his academic career at Harvard Medical School before being recruited in 2004 as professor and chair of the department of urology at Wake Forest School of Medicine. After moving his laboratory from Boston, he became the founding Director of the Wake Forest Institute for Regenerative Medicine, where his research and work has produced extraordinary results for nearly two decades.

About the American College of Surgeons The American College of Surgeons is a scientific and educational organization of surgeons that was founded in 1913 to raise the standards of surgical practice and improve the quality of care for all surgical patients. The College is dedicated to the ethical and competent practice of surgery. Its achievements have significantly influenced the course of scientific surgery in America and have established it as an important advocate for all surgical patients. The College has more than 84,000 members and is the largest organization of surgeons in the world. "FACS" designates that a surgeon is a Fellow of the American College of Surgeons.

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Radium was once cast as an elixir of youth. Are todays ideas any better? – Popular Science

By daniellenierenberg

From cities in the sky to robot butlers, futuristic visions fill the history ofPopSci. In theAre we there yet?column we check in on progress towards our most ambitious promises. Read the series and explore all our 150th anniversary coveragehere.

In 1923, Popular Science reported that people were drinking radium-infused water in an attempt to stay young. How far have we come to a real (and non-radioactive) cure for aging?

From the time Marie Curie and her husband Pierre discovered radium in 1898, it was quickly understood that the new element was no ordinary metal. When the Curies finally isolated pure radium from pitchblende (a mineral ore) in 1902, they determined that the substance was a million times more radioactive than uranium. At the time, uranium was already being used in medicine to X-ray bones and even treat cancer tumors, a procedure first attempted in 1899 by Tage Sjogren, a Swedish doctor. Coupled with radiums extraordinary radioactivity and unnatural blue glow, the mineral was soon touted as a cure for everything including cancer, blindness, and baldness, even though radioactivity had only been used to treat malignant tumors. As Popular Science reported in June 1923, it was even believed that a daily glassful of radium-infused water would restore youth and extend life, making it the latest in a long line of miraculous elixirs.

By May 1925 The New York Times was among the first to report cancer cases linked to radium. Two years later, five terminally ill women, who became known as the Radium Girls, sued the United States Radium Corporation where they had worked, hand-painting various objects with the companys poisonous pigment. As more evidence emerged of radiums carcinogenic effects, its cure-all reputation quickly faded, although it would take another half-century before the last of the luminous-paint processing plants was shut down. Radium is still used today in nuclear medicine to treat cancer patients, and in industrial radiography to X-ray building materials for structural defectsbut its baseless status as a life-extending elixir was short-lived.

And yet, radiums downfall did not end the true quest for immortality: Our yearning for eternal youth continues to inspire a staggering range of scientifically dubious products and services.

Since the early days of civilization, when Sumerians etched one of the first accounts of a mortal longing for eternal life in the Epic of Gilgamesh on cuneiform tablets, humans have sought a miracle cure to defy aging and defer death. Five thousand years ago in ancient Egypt, priests practiced corpse preservation so a persons spirit could live on in its mummified host. Fortunately, anti-aging biotech has advanced from mummification and medieval quests for the fountain of youth, philosophers stone, and holy grail, as well as the perverse practices of sipping metal-based elixirs, bathing in the blood of virgins, and even downing Radium-infused water in the early 20th century. But what hasnt changed is that the pursuit of eternal youth has largely been sponsored by humankinds wealthiest citizens, from Chinese emperors to Silicon Valley entrepreneurs.

Weve all long recognized that aging is the greatest risk factor for the overwhelming majority of chronic diseases, whether it be Alzheimers disease, cancer, osteoporosis, cardiovascular diseases, or diabetes, says Nathan LeBrasseur, co-director of The Paul F. Glenn Center for Biology of Aging Research at the Mayo Clinic in Minnesota. But weve really kind of said, well, theres nothing we can do about senescence [cellular aging], so lets move on to more prevalent risk factors that we think we can modify, like blood pressure or high lipids. In the last few decades, however, remarkable breakthroughs in aging research have kindled interest and opened the funding spigots. Fortunately, the latest efforts have been grounded in more established scienceand scientific methodsthan was available in radiums heyday.

In the late 19th century, just as scientists began zeroing in on germs with microscopes, evolutionary biologist August Weismann delivered a lecture on cellular aging, or senescence. The Duration of Life (1881) detailed his theory that cells had replication limits, which explained why the ability to heal diminished with age. It would take 80 years to confirm Weismanns theory. In 1961, biologists Leonard Hayflick and Paul Moorhead observed and documented the finite lifespan of human cells. Another three decades later, in 1993, Cynthia Kenyon, a geneticist and biochemistry professor at the University of California, San Francisco, discovered how a specific genetic mutation in worms could double their lifespans. Kenyons discovery gave new direction and hope to the search for eternal youth, and wealthy tech entrepreneurs were eager to fund the latest quest: figuring out how to halt aging at the cellular level. (Kenyon is now vice president of Calico Research Labs, an Alphabet subsidiary.)

Weve made such remarkable progress in understanding the fundamental biology of aging, says LeBrasseur. Were at a new era in science and medicine, of not just asking the question, what is it about aging that makes us at risk for all these conditions? But also is there something we can do about it? Can we intervene?

In modern aging research labs, like LeBrasseurs, the focus is to tease apart the molecular mechanisms of senescence and develop tools and techniques to identify and measure changes in cells. The ultimate goal is to discover how to halt or reverse the changes at a cellular level.

But the focus on the molecular mechanisms of aging is not new. In his 1940 book, Organisers and Genes, theoretical biologist Conrad Waddington offered a metaphor for a cells life cyclehow it grows from an embryonic state to something specific. In Waddingtons epigenetic landscape, a cell starts out in its unformed state at the top of a mountain with the potential to roll downhill in any direction. After encountering a series of forks, the cell lands in a valley, which represents the tissue it becomes, like a skin cell or a neuron. According to Waddington, epigenetics are the external mechanisms of inheritanceabove and beyond standard genetics, such as chemical or environmental factorsthat lead the cell to roll one way or another when it encounters a fork. Also according to Waddington, who first proposed the theory of epigenetics, once the cell lands in its valley, it will remain there until it diesso, once a skin cell, always a skin cell. Waddington viewed cellular aging as a one-way journey, which turns out to be not so accurate.

We know now that even cells of different types keep changing as they age, says Morgan Levine, who until recently led her own aging lab at the Yale School of Medicine, but is now a founding principal investigator at Altos Labs, a lavishly funded startup. The [Waddington] landscape keeps going. And the new exciting thing is reprogramming, which shows us that you can push the ball back the other way.

Researchers like Levine continue to discover new epigenetic mechanisms that can be used to not only determine a cells age (epigenetic or biological clock) but also challenge Waddingtons premise that a cells life is one way. Cellular reprogramming is an idea first attempted in the 1980s and later advanced by Nobel Prize recipient Shinya Yamanaka, who discovered how to revert mature, specialized cells back to their embryonic, or pluripotent, state, enabling them to start fresh and regrow, for instance, into new tissue like liver cells or teeth.

I like to think of the epigenome as the operating system of a cell, Levine explains. So more or less all the cells in your body have the same DNA or genome. But what makes the skin cell different from a brain cell is the epigenome. It tells a cell which part of the DNA it should use thats specific to it. In sum, all cells start out as embryonic or stem cells, but what determines a cells end state is the epigenome.

Theres been a ton of work done with cells in a dish, Levine adds, including taking skin cells from patients with Alzheimers disease, converting them back to stem cells, and then into neurons. For some cells, you dont always have to go back to the embryonic stem cell, you can just convert directly to a different cell type, Levine says. But she also notes that what works in a dish is vastly different from what works in living specimens. While scientists have experimented with reprogramming cells in vivo in lab animals with limited success, the ramifications are not well understood. The problem is when you push the cells back too far [in their life cycle], they dont know what theyre supposed to be, says Levine. And then they turn into all sorts of nasty things like teratoma tumors. Still, shes hopeful that many of the problems with reprogramming may be sorted out in the next decade. Levine doesnt envision people drinking cellular-reprogramming cocktails to stave off agingat least not in the foreseeable futurebut she does see early-adopter applications for high-risk patients who, lets say, can regrow their organs instead of requiring transplants.

While the quest for immortality is still funded largely by the richest of humans, it has morphed from the pursuit of mythical objects, miraculous elements, and mystical rituals to big business, raising billions to fund exploratory research. Besides Calico and Altos Labs (funded by Russian-born billionaire Yuri Milner and others), theres Life Biosciences, AgeX Therapeutics, Turn Biotechnologies, Unity Biotechnology, BioAge Labs, and many more, all founded in the last decade. While theres considerable hype for these experimental technologies, any actual products and services will have to be approved by regulatory agencies like the Food and Drug Administration, which did not exist when radium was being promoted as a cure-all in the US.

While were working on landing long-term moon shots like editing genomes with CRISPR and reprogramming epigenomes to halt or reverse aging, LeBrasseur sees near-term possibilities in repurposing existing drugs to prop up senescent cells. When a cell gets old and damaged, it has one of three choices: to succumb, in which case it gets flushed from the system; to repair itself because the damage is not so bad; or to stop replicating and hang around as a zombie cell. Not only do [zombie cells] not function properly, explains LeBrasseur, but they secrete a host of very toxic molecules known as senescence associated secretory phenotype, or SASP. Those toxic molecules trigger inflammation, the precursor to many diseases.

It turns out there are drugs, originally targeted at other diseases, that are already in anti-aging trials because theyve shown potential to impact cell biology at a fundamental level, effectively staving off senescence. Although rapamycin was originally designed to suppress the immune system in organ transplant patients, and metformin to assist diabetes patients, both have shown anti-aging promise. When you start looking at data from an epidemiological lens, you recognize that these individuals [like diabetes patients taking metformin] often have less cardiovascular disease, notes LeBrasseur. They also have lower incidence of cancer, and theres some evidence that they may even have lower incidence of Alzheimers disease. Even statins (for cardiovascular disease) and SGL2 inhibitors (another diabetes drug) are being explored for a possible role in anti-aging. Of course, senescence is not all bad. It plays an important role, for example, as a protective mechanism against the development of malignant tumorsso tampering with it could have its downsides. Biology is so smart that weve got to stay humble, right? says LeBrasseur.

Among other things, the Radium Girls taught us to avoid the hype and promise of new and unproven technologies before the pros and cons are well understood. Weve already waited millennia for a miracle elixir, making some horrific choices along the way, including drinking radioactive water as recently as a century ago. The 21st century offers its own share of anti-aging quackery, including unregulated cosmetics, questionable surgical procedures, and unproven dietary supplements. While we may be closer than weve ever been in human history to real solutions for the downsides of aging, there are still significant hurdles to overcome before we can reliably restore youth. It will take years or possibly decades of research, followed by extensive clinical trials, before todays anti-aging research pays dividendsand even then its not likely to come in the form of a cure-all cocktail capable of bestowing immortality. In the meantime, LeBrasseurs advice is simple for those who can afford it: You dont have to wait for a miracle cure. Lifestyle choices like physical activity, nutritional habits, and sleep play a powerful role on our trajectories of aging. You can be very proactive today about how well you age. Unfortunately, not everyone has the means to follow LeBrasseurs medical wisdom. But the wealthiest among usincluding those funding immortalitys questmost definitely do.

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Stem Cells: A Case for the Use of Human Embryos in Scientific Research

By daniellenierenberg

ABSTRACT

Embryonic stem cells have immense medical potential. While both their acquisition for and use in research are fraught with controversy, arguments against their usage are rebutted by showing that embryonic stem cells are not equivalent to human lives. It is then argued that not using human embryos is unethical. Finally, an alternative to embryonic stem cells is presented.

Embryonic stem cells have the potential to cure nearly every disease and condition known to humanity. Stem cells are natures Transformers. They are small cells that can regenerate indefinitely, waiting to transform into a specialized cell type such as a brain cell, heart cell or blood cell [1]. Most stem cells form during the earliest stages of human development, immediately when an embryo is formed. These cells, known as embryonic stem cells (ESCs), eventually develop into every single type of cell in the body. As the embryo develops, adult stem cells (ASCs) replace these all-powerful embryonic stem cells. ASCs can only become a number of different cells within their potency. This limited application means an adult mesenchymal stem cell cannot become a neural cell.

By harnessing the unique ability of embryonic stem cells to transform into functional cells, scientists can develop treatments for a number of diseases and injuries, according to the California Institute for Regenerative Medicine, a private organization which awards grants for stem cell research [1]. For example, scientists at the Cleveland Clinic converted ESCs into heart muscle cells and injected them into patients who suffered from heart attacks. The cells continued to grow and helped the patients hearts recover [2].

With this enormous potential to cure devastating diseases, including heart failure, spinal cord injuries and Alzheimers disease, governments and research organizations have the moral imperative to support and encourage embryonic stem cell research. President Barack Obama signed an executive order in 2009 loosening federal funding restrictions on stem cell research, saying, We will aim for America to lead the world in the discoveries it one day may yield. [3]. The National Institute of Health and seven state governments, including California, Maryland and New York, followed Obamas lead by creating programs that offered over $5 billion in funding and other incentives to scientists and research institutions for stem cell research [4].

Scientists believe that harnessing the capability of embryonic stem cells will unlock the cure for countless diseases. I am very excited about embryonic stem cells, said Dr. Dieter Egli, professor of developmental cell biology at Columbia University. They will lead to unprecedented discoveries that will transform life. I have no doubt about it. [5]. The results thus far are inspiring. In 2016, Kris Boesen, a 21-year-old college student from Bakersfield, California, suffered a severe spinal cord injury in a car accident that left him paralyzed from the neck down. In a clinical trial conducted by Dr. Charles Liu at the University of Southern California Keck School of Medicine, Boesen was injected with 10 million embryonic stem cells that transformed into nerve cells [6]. Three months after the treatment, Boesen regained the use of his arms and hands. He could brush his teeth, operate a motorized wheelchair, and live more independently. All Ive wanted from the beginning was a fighting chance, he said. The power of stem cells made his wish possible [6].

Embryonic stem cell treatments may also cure type 1 diabetes. Type 1 diabetes, which affects 42 million worldwide, is an autoimmune disorder that results in the destruction of insulin-producing beta cells found in the pancreas [7]. ViaCyte, a company in San Diego, California, is developing an implant that contains replacement beta cells originating from embryonic stem cells [7]. The implant will preserve or replace the original beta cells to protect them from the patients immune system [7]. The company believes that if successful, this strategy will effectively cure type 1 diabetes. Patients with the disease will no longer have to closely monitor their blood sugar levels and inject insulin [7]. ViaCyte projects that an experimental version of this implant will become available by 2020 [7].

Ultimately, scientists believe they will grow complex organs using stem cells within the next decade [8]. Over 115,000 people in the United States need a life-saving organ donation, and an average of 20 people die every day due to the lack of available organs for transplant, according to the American Transplant Foundation [9]. Three-dimensional printing of entire organs derived from stem cells holds the most promise for solving the organ shortage crisis [8]. Researchers at the University of California, San Diego have successfully printed part of a functional liver [8]. While the printed liver is not ready for transplant, it still performs the functions of a normal liver. This has helped scientists reduce the need for often cruel and unethical animal testing. The scientists expose drugs to the printed liver and observe how it reacts. The livers response closely mimics that of a human beings and no living animals are harmed in the process [8].

Research using embryonic stems cells provides an unprecedented understanding of human development and the potential to cure devastating diseases. However, stem cell research has generated controversy among religious organizations such as the Catholic Church as well as the pro-life movement [3]. That is because scientists harvest stem cells from embryos donated by fertility clinics. Opponents of embryonicstem cell research equate the destruction of an embryo to the murder of an innocent human being [10]. Pope Benedict XVI said that harvesting stem cells is not only devoid of the light of God but is also devoid of humanity [3]. However, this view does not reflect a reasonable understanding and interpretation of basic biology. Researchers typically harvest embryonic stem cells from an embryo five days after fertilization [1]. At this stage, the entire embryo consists of less than 250 cells, smaller than the tip of a pin. Of these cells, only 30 are embryonic stem cells, which cannot perform any human function [11]. For comparison, an adult has more than 72 trillion cells, each with a specialized function [3]. Therefore, this microscopic blob of cells in no way represents human life.

With no functional cells, there exist no characteristics of a human being. Fundamentalist Christians believe that the presence or absence of a heartbeat signifies the beginning and end of a human life [10]. However, at this stage there is no heart, not even a single heart cell [10]. Some contend that brain activity, or the ability to feel, defines a human being. Michael Gazzaniga, president of the Cognitive Neuroscience Institute at the University of California, Santa Barbara, explains in his book,The Ethical Brain,that the fertilized egg is a clump of cells with no brain. [12]. There is no brain nor nerve cells that could allow this cellular object to interact with its environment [12]. The only uniquely human feature of embryonic cells at this stage is that they contain human DNA. This means that a 5-day-old human embryo is effectively no different than the Petri dishes of human cells that have grown in laboratories for decades with no controversy or opposition. Therefore, if the cluster of cells in the earliest stage of a human embryo is considered a human life, a growing plate of skin cells must also be considered human life. Few would claim that a Petri dish of human cells is morally equivalent to a living human or any other animal. Why, then, would a microscopic collection of embryonic cells have the same moral status as an adult human?

The status of the human embryo comes from itspotentialto turn into a fully grown human being. However, the potential of this entity to become an individual does not logically mean that it has the same status as an individual who can think and feel. If this were true, virtually every cell grown in a laboratory would be subject to the same controversy. This is because scientists have developed technology to convert an ordinary cell such as a skin cell into an embryo [10]. Although this requires a laboratory with special conditions, the normal development of a human being also requires special conditions in the womb of the mother. Therefore, almost any cell could be considered a potential individual, so it is illogical to conclude that a cluster of embryonic cells deserves a higher moral status.

Hundreds of thousands of embryos are destroyed each year in a process known as in vitro fertilization (IVF), a popular procedure that helps couples have children [13]. Society has an ethical obligation to use these discarded embryos to make medical advancements rather than simply throw them in the trash for misguided ideological and religious reasons as opponents of embryonic stem cell research desire.

With IVF, a fertility clinician harvests sperm and egg cells from the parents and creates an embryo in a laboratory before implanting it in the womans womb. However, creating and implanting a single embryo is expensive and often leads to unsuccessful implantation. Instead, the clinician typically creates an average of seven embryos and selects the healthiest few to implant [13].

This leaves several unused embryos for every one implanted. The couple can pay a fee to preserve the unused embryos by freezing them or can donate them to another family. Otherwise, they are slated for destruction [14]. A 2011 study in the Journal of the American Society for Reproductive Medicine found that 19 percent of the unused embryos are discarded and only 3 percent are donated for scientific research [14]. Many of these embryos could never grow into a living person given the chance because they are not healthy enough to survive past early stages of development [14]. If a human embryo is already destined for destruction or has no chance of survival, scientists have the ethical imperative to use these embryos to research and develop medical treatments that could save lives. The modern version of the Hippocratic oath states, I will apply, for the benefit of the sick, all measures which are required [to heal] [10]. Republican Senator Orrin Hatch of Utah supports the pro-life movement, which recognizes early embryos as human individuals. However, even he favors using the leftover embryos for the greater good. The morality of the situation dictates that these embryos, which are routinely discarded, be used to improve and save lives. The tragedy would be in not using these embryos to save lives when the alternative is that they would be discarded. [3]

Although scientists have used embryonic stem cells (ESCs) for promising treatments, they are not ideal, and scientists hope to eliminate the need for them. Primarily, ESCs come from an embryo with different DNA than the patient who will receive the treatment, meaning they are not autologous. ESCs are not necessarily compatible with everyone and could cause the immune system to reject the treatment [11]. The most promising alternative to ESCs are known as induced pluripotent stem cells. In 2008, scientists discovered a way to reprogram human skin cells to embryonic stem cells [15]. Scientists easily obtained these cells from a patients skin, converted them into the desired cell type, then transplanted them into the diseased organ without risk of immune rejection [15]. This eliminates any ethical concerns because no embryos are harvested or destroyed in the process. However, induced stem cells have their own risks. Recent studies have shown that they can begin growing out of control and turn into cancer [3]. Several of the first clinical trials with induced stem cells, including one aimed at curing blindness by regenerating a patients retinal cells, were halted because potentially cancerous mutations were detected [3].

Scientists believe that induced stem cells created in a laboratory will one day completely replace embryonic stem cells harvested from human embryos. However, the only way to create perfect replicas of ESCs is to thoroughly understand their structure and function. Scientists still do not completely understand how ESCs work. Why does a stem cell sometimes become a nerve cell, sometimes become a heart cell and other times regenerate to produce another stem cell? How can we tell a stem cell what type of cell to become? To develop a viable alternative to ESCs, scientists must first answer these questions with experiments on ESCs from human embryos. Therefore, extensive embryonic stem cell research today will eliminate the need for embryonic stem cells in the future.

The Biomedical Engineering Society Code of Ethics calls upon engineers to use their knowledge, skills, and abilities to enhance the safety, health and welfare of the public. [16] Stem cell research epitomizes this. Stem cells hold the cure for numerous diseases ranging from spinal cord injuries to organ failure and have the potential to transform modern medicine. Therefore, the donation of human embryos to scientific research falls within most conventional ethical frameworks and should be allowed with minimal restriction.

Because of widespread ignorance about the science behind stem cells, ill-informed opposition has prevented scientists from receiving the funding and support they need to save millions of lives. For example, George W. Bushs religious opposition to stem cell research resulted in a 2001 law severely limiting government funding for such research [3]. Although most opponents of stem cell research compare the destruction of a human embryo to the death of a living human, the biology of these early embryos is no more human than a plate of skin cells in a laboratory. Additionally, all embryos sacrificed for scientific research would otherwise be discarded and provide no benefit to society. If society better understood the process and potential of embryonic stem cell research, more people would surely support it.

Within the next decade, stem cells will likely provide simple cures for diseases that are currently untreatable, such as Alzheimers disease and organ failure [1]. As long as scientists receive support for embryonic stem cell research, stem cell therapies will become commonplace in clinics and hospitals around the world. Ultimately, the fate of this new medical technology lies in the hands of the public, who must support propositions that will continue to allow and expand the impact of embryonic stem cell research.

By Jonathan Sussman, Viterbi School of Engineering, University of Southern California

At the time of writing this paper, Jonathan Sussman was a senior at the University of Southern California studying biomedical engineering with an emphasis in biochemistry. He was an undergraduate research assistant in the Graham Lab investigating proteomics of cancer cells and was planning to attend an MD/PhD program.

[1] Stem Cell Information,Stem Cell Basics, 2016. [Online]. Available at:https://stemcells.nih.gov/info/basics/3.htm%5BAccessed 11 Oct. 2018].

[2] Cleveland Clinic, Stem Cell Therapy for Heart Disease | Cleveland Clinic, 2017. [Online]. Available at:https://my.clevelandclinic.org/health/diseases/17508-stem-cell-therapy-for-heart-disease%5BAccessed 14 Oct. 2018].

[3] B. Lo and L. Parham, Ethical Issues in Stem Cell Research,Endocrine Reviews, 30(3), pp.204-213, 2009.

[4] G. Gugliotta,Why Many States Now Have Stem Cell Research Programs, 2015. [Online]. Available at:http://www.governing.com/topics/health-human-services/last-decades-culture-wars-drove-some-states-to-fund-stem-cell-research.html%5BAccessed 14 Oct. 2018].

[5] D. Cyranoski,How human embryonic stem cells sparked a revolution,Nature Journal, 2018. [Online]. Available at:https://www.nature.com/articles/d41586-018-03268-4%5BAccessed 11 Oct. 2018].

[6] K. McCormack,Young man with spinal cord injury regains use of hands and arms after stem cell therapy, The Stem Cellar, 2016. [Online]. Available at:https://blog.cirm.ca.gov/2016/09/07/young-man-with-spinal-cord-injury-regains-use-of-hands-and-arms-after-stem-cell-therapy/%5BAccessed 11 Oct. 2018].

[7] A. Coghlan,First implants derived from stem cells to cure type 1 diabetes,New Scientist, 2017. [Online]. Available at:https://www.newscientist.com/article/2142976-first-implants-derived-from-stem-cells-to-cure-type-1-diabetes/%5BAccessed 11 Oct. 2018].

[8] C. Scott,University of California San Diegos 3D Printed Liver Tissue May Be the Closest Weve Gotten to a Real Printed Liver,3DPrint.com | The Voice of 3D Printing / Additive Manufacturing, 2018. [Online]. Available at:https://3dprint.com/118932/uc-san-diego-3d-printed-liver/%5BAccessed 11 Oct. 2018].

[9] American Transplant Foundation,Facts and Myths about Transplant. [Online]. Available at:https://www.americantransplantfoundation.org/about-transplant/facts-and-myths/%5BAccessed 11 Oct. 2018].

[10] A. Siegel, Ethics of Stem Cell Research,Stanford Encyclopedia of Philosophy, 2013. [Online]. Available at:https://plato.stanford.edu/entries/stem-cells/%5BAccessed 11 Oct. 2018].

[11] I. Hyun,Stem Cells The Hastings Center,The Hastings Center, 2018. [Online]. Available at:https://www.thehastingscenter.org/briefingbook/stem-cells/%5BAccessed 11 Oct. 2018].

[12] M. Gazzaniga,The Ethical Brain,New York: Harper Perennial, 2006.

[13] M. Bilger,Shocking Report Shows 2.5 Million Human Beings Created for IVF Have Been Killed | LifeNews.com,LifeNews, 2016. [Online]. Available at:https://www.lifenews.com/2016/12/06/shocking-report-shows-2-5-million-human-beings-created-for-ivf-have-been-killed/%5BAccessed 11 Oct. 2018].

[14] Harvard Gazette, Stem cell lines created from discarded IVF embryos, 2008. [Online]. Available at:https://news.harvard.edu/gazette/story/2008/01/stem-cell-lines-created-from-discarded-ivf-embryos/%5BAccessed 11 Oct. 2018].

[15] K. Murray,Could we make babies from only skin cells?, CNN, 2017. [Online]. Available at:https://www.cnn.com/2017/02/09/health/embryo-skin-cell-ivg/index.html%5BAccessed 11 Oct. 2018].

[16] Biomedical Engineering Society,Biomedical Engineering Society Code of Ethics, 2004. [Online]. Available at:https://www.bmes.org/files/CodeEthics04.pdf%5BAccessed 11 Oct. 2018].

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Stem Cells: A Case for the Use of Human Embryos in Scientific Research

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Human Embryonic Stem Cells | The Embryo Project Encyclopedia

By daniellenierenberg

Human Embryonic Stem Cells

Stem cells are undifferentiated cells that are capable of dividing for long periods of time and can give rise to specialized cells under particular conditions. Embryonic stem cells are a particular type of stem cell derived from embryos. According to US National Institutes of Health (NIH), in humans, the term embryo applies to a fertilized egg from the beginning of division up to the end of the eighth week of gestation, when the embryo becomes a fetus. Between fertilization and the eighth week of gestation, the embryo undergoes multiple cell divisions. At the eight-cell stage, roughly the third day of division, all eight cells are considered totipotent, which means the cell has the capability of becoming a fully developed human being. By day four, cells begin to separate and form a spherical layer which eventually becomes the placenta and tissue that support the development of the future fetus. A mass of about thirty cells, called the inner cell mass, forms at one end of the sphere and eventually becomes the body. When the sphere and inner cell mass are fully formed, around day 5, the pre-implantation embryo is referred to as a blastocyst. At this point the cells in the inner cell mass have not yet differentiated, but have the ability to develop into any specialized cell type that makes up the body. This property is known as pluripotency. As of 2009, embryonic stem cells refer to pluripotent cells that are generally derived from the inner cell mass of blastocysts.

In November 1998, two independent publications announced the first successful isolation and culture of pluripotent human stem cells. While working at the Wisconsin National Primate Research Center, located at the University of Wisconsin-Madison, James A. Thomson and his team of researchers cultured human embryonic stem cells from the inner cell mass of donated embryos originally produced for in vitro fertilization. The characteristics of the cultured cells were consistent with previously identified features in animal stem cells. They were capable of long-term self-renewal and thus could remain undifferentiated for long periods of time; they had particular surface markers; and they were able to maintain a normal and stable karyotype. Thomsons team also observed derivatives of all the three germ layersendoderm, mesoderm, and ectoderm. Since the three germ layers precede differentiation into all the cell types in the body, this observation suggested that the cultured cells were pluripotent. The team published Embryonic Stem Cell Lines Derived from Human Blastocysts, in the 6 November Science issue. Soon afterwards, a research team led by John D. Gearhart at the Johns Hopkins School of Medicine, published Derivation of Pluripotent Stem Cells from Cultured Human Primordial Germ Cells in Proceedings of the National Academy of Science. The paper detailed the process by which pluripotent stem cells were derived from gonadal ridges and mesenteries extracted from aborted five-to-nine week old human embryos. Gearhart and his team noted the same observations as Thomsons team. Despite coming from different sources, according to NIH, the resultant cells seem to be the same.

The largest source of blastocysts for stem cell research comes from in vitro fertilization (IVF) clinics. Used for reproductive purposes, IVF usually produces an abundance of viable blastocysts. Excess blastocysts are sometimes donated for research purposes after obtaining informed consent from donors. Another potential method for producing embryonic stem cells is somatic cell nuclear transfer (SCNT). This has been successfully done using animal cells. The nucleus of a differentiated adult cell, such as a skin cell, is removed and fused with an enucleated egg, an egg with the nucleus removed. The egg, now containing the genetic material from the skin cell, is believed to be totipotent and eventually develops into a blastocyst. As of mid-2006, attempts to produce human embryonic stem cells using SCNT have been unsuccessful. Nonetheless, scientists continue to pursue this method because of the medical and scientific implications of embryonic stem cells lines with an identical genetic makeup to particular patients. One problem faced in tissue transplants is immune rejection, where the host body attacks the introduced tissue. SCNT would be a way to overcome the incompatibility problem by using the patients own somatic cells.

Recent discoveries in cultivating human embryonic stem cells may potentially lead to major advancements in understanding human embryogenesis and medical treatments. Previously, limitations in access and environmental control have stunted research initiatives aimed at mapping out the developmental process. Insights into differentiation factors may lead to treatments into such areas as birth defects. Manipulation of the differentiation process may then lead to large supplies of stem cells for cell-based therapies on patients with Parkinsons disease, for example. In theory adult stem cells can also be cultivated for such purposes, but isolating and identifying adult stem cells has been difficult and the prospects for treatment are more limited than using embryonic stem cells.

Despite the potential benefits that may come about through human embryonic stem cell research, not everyone in the public embraces it. Several ethical debates surround this newly developing research field. Much of the debate stems from differing opinions on how we should view embryos: is an embryo a person? Should an embryo be considered property? Ethical concerns in embryonic stem cell research include destroying human blastocysts, laws surrounding informed consent, and particularly for SCNT, misapplication of techniques for reproductive cloning. For the latter concern, SCNT does produce a blastocyst which contains stem cell clones of an adult cell, but the desired application is in growing replacement tissues. Still, a portion of the public fears the hypothetical one day, when someone decides to use SCNT to develop and raise a human clone.

The public debate continues, advancing along with the changes in the field. As of 2006, public opinion polls showed that majority of religious and non-religious Americans now support embryonic stem cell research, but opinions remain divided over whether it is legitimate to create or use human blastocysts solely for research.

Wu, Ke, "Human Embryonic Stem Cells".

(2010-09-13). ISSN: 1940-5030 http://embryo.asu.edu/handle/10776/2055.

Arizona State University. School of Life Sciences. Center for Biology and Society. Embryo Project Encyclopedia.

Arizona Board of Regents Licensed as Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported (CC BY-NC-SA 3.0) http://creativecommons.org/licenses/by-nc-sa/3.0/

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Human Embryonic Stem Cells | The Embryo Project Encyclopedia

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North America is the largest region in the Stem Cell Therapy Market, worth $2 Billion in 2021. What does the future hold? As Per The Business Research…

By daniellenierenberg

LONDON, May 26, 2022 (GLOBE NEWSWIRE) -- According to The Business Research Companys research report on the stem cell therapy market, North America was the largest region in the stem cell therapy market and was worth $2.16 billion in 2021. The market accounted for 0.009% of the region's GDP. In terms of per capita consumption, the market accounted for $4.3, $3.8 higher than the global average. The stem cell therapy market in North America is supported by factors including the presence of key players engaged in developing stem cell therapies; advanced healthcare infrastructure; extensive research and development; supportive reforms from healthcare organizations; and strong reimbursement policies. For instance, companies are collaborating from different parts of the world to fund and develop new methods for stem cell therapy. In 2021, RxCell, a USA-based biotechnology company specializing in stem cell therapy, will collaborate with the Agency for Science, Technology, and Research (A*STAR)s Institute of Molecular and Cell Biology (IMCB) to co-fund and develop cellular therapeutics for age-related diseases.The Agency for Science, Technology, and Research (A*STAR)s Institute of Molecular and Cell Biology (IMCB) is a Singaporean biotechnology institute.

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The global stem cell therapy market size is expected to grow from $10.67 billion in 2021 to $11.99 billion in 2022 at a compound annual growth rate (CAGR) of 12.4%. The growth in the market is mainly due to the companies resuming their operations and adapting to the new normal while recovering from the COVID-19 impact, which had earlier led to restrictive containment measures involving social distancing, remote working, and the closure of commercial activities that resulted in operational challenges. The stem cell therapy market is expected to reach $21.17 billion in 2026 at a CAGR of 15.3%.

To sustain product innovation in an increasingly competitive market, major companies in the animal stem cell therapy market as well as the placental stem cell therapy market are undertaking strategic initiatives such as collaborations, partnerships, and acquisitions. The advantages of strategic partnerships include sharing of resources, expansion of distribution, and promotion of products. For instance, in June 2021, Catalent, a New Jersey-based pharmaceutical company involved with gene therapies, announced the acquisition of RheinCell Therapeutics, a company specializing in the GMP-compliant generation of human-induced pluripotent stem cells (iPS cells) and therapies, for an undisclosed amount. Through this acquisition, Catalent further strengthens its cell therapy portfolio and offers enhanced iPSC-based cell therapy capabilities. RheinCell Therapeutics is headquartered in Langenfeld, Germany, and was founded in 2017. In June 2020, Century Therapeutics, a US based developer of induced pluripotent stem cell-derived allogeneic cell therapies, announced the acquisition of Empirica Therapeutics for an undisclosed amount. This acquisition will leverage Century Therapeutics' iPSC-derived allogeneic cell therapies against glioblastoma (GBM). Empirica Therapeutics is a Canada-based developer of therapeutic drugs designed to treat aggressive forms of cancer.

Major players in the stem cell therapy market are Anterogen, JCR Pharmaceuticals, Medipost, Osiris Therapeutics, Pharmicell, Astellas Pharma, Cellectis, Celyad, Novadip Biosciences, Gamida Cell, Capricor Therapeutics, Cellular Dynamics, CESCA Therapeutics, DiscGenics, OxStem, Mesoblast, ReNeuron Group, Takeda Pharmaceuticals, Magellan, Kolon TissueGene, Stemedica Cell Technologies, Holostem Terapie Avanzate S.r.l., NuVasive, RTI Surgical, and AlloSource.

The global stem cell therapy market is segmented by type into allogeneic stem cell therapy, autologous stem cell therapy; by cell source into adult stem cells, induced pluripotent stem cells, embryonic stem cells; by application into musculoskeletal disorders, wounds and injuries, cancer, autoimmune disorders, others; by end-user into hospitals, clinics.

The Middle East is expected to be the fastest growing region in the forecast period. The regions covered in the stem cell market analysis report are Asia-Pacific, Western Europe, Eastern Europe, North America, South America, the Middle East, and Africa.

Stem Cell Therapy Global Market Report 2022 Market Size, Trends, And Global Forecast 2022-2026 is one of a series of new reports from The Business Research Company that provide stem cell therapy market overviews, stem cell therapy market analyze and forecast market size and growth for the whole market, stem cell therapy market segments and geographies, stem cell therapy market trends, stem cell therapy market drivers, stem cell therapy market restraints, stem cell therapy market leading competitors revenues, profiles and market shares in over 1,000 industry reports, covering over 2,500 market segments and 60 geographies.

The report also gives in-depth analysis of the impact of COVID-19 on the market. The reports draw on 150,000 datasets, extensive secondary research, and exclusive insights from interviews with industry leaders. A highly experienced and expert team of analysts and modelers provides market analysis and forecasts. The reports identify top countries and segments for opportunities and strategies based on market trends and leading competitors approaches.

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North America is the largest region in the Stem Cell Therapy Market, worth $2 Billion in 2021. What does the future hold? As Per The Business Research...

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Does it matter whose brain cells we use in gadgets of the future? – The Next Web

By daniellenierenberg

The year is 2030 and we are at the worlds largest tech conference, CES in Las Vegas. A crowd is gathered to watch a big tech company unveil its new smartphone. The CEO comes to the stage and announces the Nyooro, containing the most powerful processor ever seen in a phone. The Nyooro can perform an astonishing quintillion operations per second, which is a thousand times faster than smartphone models in 2020. It is also ten times more energy-efficient with a battery that lasts for ten days.

A journalist asks: What technological advance allowed such huge performance gains? The chief executive replies: We created a new biological chip using lab-grown human neurons. These biological chips are better than silicon chips because they can change their internal structure, adapting to a users usage pattern and leading to huge gains in efficiency.

Another journalist asks: Arent there ethical concerns about computers that use human brain matter?

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Although the name and scenario are fictional, this is a question we have to confront now. In December 2021, Melbourne-based Cortical Labs grew groups of neurons (brain cells) that were incorporated into a computer chip. The resulting hybrid chip works because both brains and neurons share a common language: electricity.

In silicon computers, electrical signals travel along metal wires that link different components together. In brains, neurons communicate with each other using electric signals across synapses (junctions between nerve cells). In Cortical Labs Dishbrain system, neurons are grown on silicon chips. These neurons act like the wires in the system, connecting different components. The major advantage of this approach is that the neurons can change their shape, grow, replicate, or die in response to the demands of the system.

Dishbrain could learn to play the arcade game Pong faster than conventional AI systems. The developers of Dishbrain said: Nothing like this has ever existed before It is an entirely new mode of being. A fusion of silicon and neuron.

Cortical Labs believes its hybrid chips could be the key to the kinds of complex reasoning that todays computers and AI cannot produce. Another start-up making computers from lab-grown neurons, Koniku, believes their technology will revolutionize several industries including agriculture, healthcare, military technology and airport security. Other types of organic computers are also in the early stages of development.

While silicon computers transformed society, they are still outmatched by the brains of most animals. For example, a cats brain contains 1,000 times more data storage than an average iPad and can use this information a million times faster. The human brain, with its trillion neural connections, is capable of making 15 quintillion operations per second.

This can only be matched today by massive supercomputers using vast amounts of energy. The human brain only uses about 20 watts of energy, or about the same as it takes to power a lightbulb. It would take 34 coal-powered plants generating 500 megawatts per hour to store the same amount of data contained in one human brain in modern data storage centers.

Companies do not need brain tissue samples from donors, but can simply grow the neurons they need in the lab from ordinary skin cells using stem cell technologies. Scientists can engineer cells from blood samples or skin biopsies into a type of stem cell that can then become any cell type in the human body.

However, this raises questions about donor consent. Do people who provide tissue samples for technology research and development know that it might be used to make neural computers? Do they need to know this for their consent to be valid?

People will no doubt be much more willing to donate skin cells for research than their brain tissue. One of the barriers to brain donation is that the brain is seen as linked to your identity. But in a world where we can grow mini-brains from virtually any cell type, does it make sense to draw this type of distinction?

If neural computers become common, we will grapple with other tissue donation issues. In Cortical Labs research with Dishbrain, they found human neurons were faster at learning than neurons from mice. Might there also be differences in performance depending on whose neurons are used? Might Apple and Google be able to make lightning-fast computers using neurons from our best and brightest today? Would someone be able to secure tissues from deceased geniuss like Albert Einstein to make specialized limited-edition neural computers?

Such questions are highly speculative but touch on broader themes of exploitation and compensation. Consider the scandal regarding Henrietta Lacks, an African-American woman whose cells were used extensively in medical and commercial research without her knowledge and consent.

Henriettas cells are still used in applications which generate huge amounts of revenue for pharmaceutical companies (including recently to develop COVID vaccines. The Lacks family still has not received any compensation. If a donors neurons end up being used in products like the imaginary Nyooro, should they be entitled to some of the profit made from those products?

Another key ethical consideration for neural computers is whether they could develop some form of consciousness and experience pain. Would neural computers be more likely to have experiences than silicon-based ones? In the Pong experiment, Dishbrain is exposed to noisy and unpredictable stimuli when it gets a response wrong (the paddle misses the ball), and predictable stimuli when it gets it right. It is at least possible that a system like this might start to experience the unpredictable stimuli as pain, and the predictable stimuli as pleasure.

Chief scientific officer Brett Kagan for Cortical Labs said:

Fully informed donor consent is of paramount importance. Any donor should have the opportunity to reach an agreement for compensation as part of this process and their bodily autonomy respected without coercion.

As recently discussed in a study there is no evidence neurons on a dish have any qualitative or conscious experience so cannot be distressed and without pain receptors, cannot feel pain. Neurons have evolved to process information of all kinds being left completely unstimulated, as currently done all over the world in labs, is not a natural state for a neuron. All this work does is allow neurons to behave as nature intended at their most basic level.

Humans have used animals to do physical labor for thousands of years, despite often leading to negative experiences for the animals. Would using organic computers for cognitive labor be any more ethically problematic than using an ox to pull a cart?

We are in the early stages of neural computing and have time to think through these issues. We must do so before products like the Nyooro move from science fiction to the shops.

This article by Julian Savulescu, Visiting Professor in Biomedical Ethics, Murdoch Childrens Research Institute; Distinguished Visiting Professor in Law, University of Melbourne; Uehiro Chair in Practical Ethics, University of Oxford; Christopher Gyngell, Research Fellow in Biomedical Ethics, The University of Melbourne, and Tsutomu Sawai, Associate Professor, Humanities and Social Sciences, Hiroshima University, is republished from The Conversation under a Creative Commons license. Read the original article.

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New Technique Turns Back the Aging Clock by 30 Years – Gilmore Health News

By daniellenierenberg

Researchers from the Babraham Institute in Cambridge, United Kingdom have revealed a new method that can make it possible to reverse aging considerably.

This novel technique can time jump skin cells by around 30 years, according to the research team. The number of years is notably longer than what earlier reprogramming techniques had managed.

Read Also: A Study of Naked Mole-Rats Gives New Insights on the Aging Process

Findings from this study have the potential of transforming regenerative medicine, which aims to fix or replace old or worn-out cells. They could promote a more focused approach to fighting aging.

The research appeared in eLife, a peer-reviewed biomedical and life sciences journal.

Stem cells are at the core of regenerative medicine, which is also sometimes called stem cell therapy. They help in repairing or replacing injured, dysfunctional, or diseased cells or tissue. They can transform into any specialized cells.

Regenerative medicine researchers have also been exploring for years how to reserve the process that is, converting specialized cells to stem cells. They have developed ways to create what are called induced stem cells, key tools in regenerative biology.

Read Also: Anti-Aging Research: Researchers Identify the Regulators of Skin Aging

While helpful for many things, stem cells can also cause problems. They could, for instance, lead to cancers through wild cell multiplication. It is, therefore, valuable to be able to reprogram induced stem cells back to the specialized cells they are from.

However, scientists have found it difficult to re-differentiate stem cells back into specialized cells. The new method in the current study helps to overcome the existing challenge.

The technique, which derives from the work of Professor Shinya Yamanaka, does not totally get rid of cell identity. It stops halfway through the process of reprogramming. This, thus, enabled cells to become younger and regain their youthful function.

Yamanaka, who got the 2012 Nobel Prize in Physiology or Medicine, discovered in 2007 a method for turning normal cells into unspecialized stem cells. The process involves four specific molecules known as the Yamanaka factors and takes about 50 days to complete.

By contrast, this new technique referred to as maturation phase transient reprogramming exposes skin cells to those molecules for only 13 days. The cells temporarily lost their identity after that. However, the partly reprogrammed cells appeared to regain markers of skin cells when allowed to grow under usual conditions.

Read Also: Study: Rapamycin May Help You Fight Skin Sagging and Wrinkles

Researchers examined measures of cellular age to confirm the rejuvenation of the cells. They looked at both the epigenetic clock and the transcriptome. Those measures indicated that the reprogrammed cells were comparable to cells that were around 30 years younger.

However, it was not just about appearance. The cells also regained youthful function.

Rejuvenated fibroblasts (skin cells) produced more collagen proteins, which provide structure to tissues and help to heal wounds. The cells also moved into areas in need of repair faster, compared to older cells. This indicates they have the potential of being used to make cells that promote more rapid wound healing.

The scientists noted that the new technique produced an effect on other genes connected to age-related disorders and symptoms. For instance, the APBA2 gene (linked to Alzheimers disease) and the MAF gene (associated with cataracts) displayed changes in youthful transcription levels.

Read Also: HGH Benefits: A Comprehensive List of Research-Backed Benefits You Could Expect from Using Growth Hormone

Future research may, therefore, open up more curative possibilities, going by these findings.

Our results represent a big step forward in our understanding of cell reprogramming, said Dr. Diljeet Gill, study co-author and a postdoc in Professor Wolf Reiks lab. We have proved that cells can be rejuvenated without losing their function and that rejuvenation looks to restore some function to old cells. The fact that we also saw a reverse of ageing indicators in genes associated with diseases is particularly promising for the future of this work.

The research team next plans to try and figure out the mechanism that underlies the successful cell reprogramming. This, scientists hope, could make it possible to promote rejuvenation without needing to reprogram but relying only on underlying regulators.

Multi-omic rejuvenation of human cells by maturation phase transient reprogramming

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Scientists are cryoconserving animals to stop them going extinct – Euronews

By daniellenierenberg

Animals at risk of extinction are having their reproductive cells stored at a major biobank, as security for their species.

Jaguar, Eastern black rhino and mountain chicken frog are some of the highly threatened species which have been given the freezing treatment by scientists at Natures SAFE, one of Europes largest biobanks of living tissue.

Small tissue samples from ovaries and testicles are taken from the animals that have passed away at Chester Zoo and, using cutting-edge technologies, cryogenically frozen at temperatures of -196C in liquid nitrogen.

Time essentially stops at this deeply low point, pausing all natural chemical processes in the cells. The frozen samples could be used in the future to resurrect a species otherwise lost on Earth.

With gene pools and animal populations continually shrinking in the wild, the work of modern conservation zoos like ours has never been more important, says Dr Sue Walker, head of science at Chester Zoo and co-founder of Natures SAFE.

Technologies, such as cryopreservation, offer us a new, critical piece of the conservation puzzle and help us provide a safeguard for many of the worlds animals that, right now, were sadly on track to lose.

More than 40,000 species are deemed to be threatened with extinction today, according to the International Union for the Conservation of Nature (IUCN). A large underestimate as only 7 per cent of the worlds species have actually been evaluated.

Human activity is known to have forced 869 species to extinction in the last 500 years, and we are now amid a biodiversity crisis that threatens to extinguish one million species of plants and animals.

Animals that pass away at the UKs largest charity zoo can still contribute to the continued existence of their species. The unique genetic code of a Javan green magpie, for example - driven to the brink of extinction by poachers - lives on in vials at the Shropshire-based biobank.

Natures SAFE outlines a number of different ways it preserves species, depending on what kind of sample is harvested.

Sperm cells can be extracted from an animals testes post-castration, before being stored in test tubes of nutrient-rich, cell-friendly anti-freeze and placed in the containers of liquid nitrogen.

The idea is that the sperm can be thawed, and used to fertilise an (also frozen) egg, with the embryo then implanted in a surrogate mother.

Ovarian and testicular tissue is also being kept indefinitely at the biobank, with scientists working on ways to make cultures from it that can produce egg and sperm cells for future breeding programmes.

Even skin cells can, under the right conditions, be reprogrammed into pluripotent stem cells - meaning they can be turned into any kind of body cell, including sperm and egg cells.

Under this pioneering method, a skin biopsy from an Eastern black rhinos ear could be the key to saving the species.

Of course, most conservationists hope the biobank will never be necessary. It is not a replacement for protecting the dwindling numbers of wildlife which still live but Tullis Matson, chair and founder of Natures SAFE says it offers a final hope.

We know the sixth mass extinction on Earth is underway, and there will be rough times ahead, he says.

The question is what do we want to do about it? And our answer is: we want to secure future options for biodiversity, by acting now.

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13 Best Hair Growth Serums Of 2022 That Actually Work – mindbodygreen.com

By daniellenierenberg

mbg Associate Beauty & Wellness Editor

mbg Associate Beauty & Wellness Editor

Jamie Schneider is the Associate Beauty & Wellness Editor at mindbodygreen, covering beauty and wellness. She has a B.A. in Organizational Studies and English from the University of Michigan, and her work has appeared in Coveteur, The Chill Times, and Wyld Skincare.

Image by Clique Images / Stocksy

May 26, 2022

If you find your hair shedding more than usual, you're not alone. Thinning happens for a number of reasons, and it's extremely common; that said, because there are so many potential causes, there are also myriad ways to naturally encourage regrowthand one popular method is to invest in a hair growth serum. The market is chock-full of products that promise thick, full-bodied strands and a thriving scalpbut which ones are actually worth your hard-earned dollars?

Here, we reveal the best hair growth serums to add to your routine. Whether you're looking to repair breakage, spot treat a sparse hairline, or just introduce some va-va-voom volume, you'll be sure to find a formula that meets your hair goals.

How do hair growth serums work?

Hair growth starts internally, with healthy hair follicles. So you may be wondering: How do topical serums work, anyway? Well, many serums include naturally derived ingredients to help stimulate the scalp (rosemary oil, lavender oil, and the like), which, in turn, deliver vital nutrients and oxygen to the hair follicle.

These serums also keep the hair you already have healthy and thriving, which is crucial when you're trying to encourage length. For example, many formulas contain antioxidants, which can help combat free radicals from UV rays or pollution. Finally, you'll find plenty of humectants and fatty-acid-rich oils to moisturize the strands and keep them strong: "The hair on your head is probably the driest thing on the body, and if you are trying to grow it longer, you need to keep it moisturized," says hairstylist Anthony Dickey regarding faster hair growth. "If your texture is naturally drier, it is even more essential to keep hair hydrated. Dry hair turns to brittle hair, and brittle hair breaks."

Healthy hair growth starts with a healthy scalp, so we specifically looked for ingredients that nourish the skin.

We made sure to include formulas that suit several strand patterns and needs.

Some serums are meant for leave-in treatments, while others are best to use pre-shampoo. Some are lightweight and absorb quickly, while others thickly glaze the strands in moisture. You'll find plenty of options here.

We tested out products firsthand to see what worked and what didn't. When this wasn't possible, our editors utilized verified customer experiences.

Considerations: Vegan, Cruelty-free, Leave-in treatment, Lightweight

This serum simply nourishes the scalp and hair with apple stem cells, which are known for their rejuvenating and antioxidant abilities; bamboo and pea extract, which help protect the strands against free radicals; and aloe vera, a star hydrator. The application itself feels like a splash of moisture, especially after a good, long rinse.

Considerations: Vegan, Cruelty-free, Leave-in treatment, Lightweight

If you're looking to "spot treat" with a hair growth serumsay, you have a sparser hairline you'd like to fillthis high-performing number is your best bet. With nicotiana benthamiana for its anti-inflammatory properties, turmeric to calm and nourish the skin, and red clover and mung bean extracts to neutralize free radicals, it's the perfect nongreasy number to nourish fragile strands.

Considerations: Vegan, Cruelty-free, Leave-in treatment, Wash-out treatment

This reviewer says it best: "I really feel like I'm treating my senses when using this for my hairthe jasmine scent is romantic and beautiful." Along with the fragrant jasmine, you'll find sunflower oil to add moisture and shine, along with amla, a classic Ayurvedic ingredient with powerful antioxidant properties.

Considerations: Vegan, Cruelty-free, Sensitive skin-safe, Leave-in treatment

You can read all about castor oil for hair here, but the fatty-acid-rich ingredient comes with a load of healthy hair benefits. The medium-weight oil is brimming with vitamin E, unsaturated fatty acids, minerals, and other antioxidants to help protect the strands from physical damage and environmental aggressors. Grab a 100% organic, naturally cold-pressed option, like Briogeo's, to wrap your tresses in a blanket of moisture.

Considerations: Vegan, Cruelty-free, Leave-in treatment, Wash-out treatment

Ever seen a hair oil so good, you thought about slathering it all over? This do-it-all serum aims to please, with a cocktail of nourishing plant and essential oils to calm and moisturize your skin and hair. It's simply a must-grab for a scalp-slash-face massagewho doesn't love a streamlined routine?

Considerations: Vegan, Cruelty-free, Leave-in treatment, Lightweight

This antioxidant-rich formula is like a tall drink of water for your scalp. Arctic root, Siberian ginseng, chaga mushroom, and red clover extracts help protect and soothe the skin up top, while peptides help support collagen production. It's super lightweight and provides a cooling experience upon application. Plus, the lightweight formula easily soaks into your strands without leaving a greasy feel.

Considerations: Vegan, Cruelty-free, Leave-in treatment

Your hair bonds can become broken over timeby heat styling, chemical processing, and other physical stressors (harsh brushing, too-tight hairstyles, and the like), which is where protein-rich repairing serums come into play: These help reconstruct those bonds, thus leading to stronger, smoother, and more defined strands. Aveda's strengthening serum contains proprietary bond-building plant molecules, along with organic avocado, green tea, and sacha inchi, and Nangai oils to deeply moisturize and further protect the strands.

Considerations: Vegan, Cruelty-free, Leave-in treatment

Moringa oil, argan oil, castor oil, and aloe vera make this simple scalp serum an absolute dream. Not to mention, the lavender aroma sets you up for a relaxing night's sleepit also helps stimulate the scalp and has even been linked to hair growth in animal studies.

Considerations: Vegan, Cruelty-free, Leave-in treatment, Wash-out treatment, Lightweight

Unless your strands tend to drink in product, chances are you'll want a lightweight leave-in serum that won't clog hair follicles or cause buildup. This Innersense formula leaves an undetectable trace, as it features dry oils (jojoba and safflower seed) that immediately sink into the strands.

Considerations: Vegan, Cruelty-free, Leave-in treatment, Lightweight

Healthy hair growth starts with a healthy, thriving scalp. Look no further than this hydrating formula, with apple stem cells, hydrolyzed lupine protein, and glycerin to soothe and protect the skin barrier. It also contains rosemarywhich boasts a number of hair growth benefitsand rosewater, which has a mildly astringent nature and can help reduce extra oil in between washes.

Considerations: Vegan, Cruelty-free, Wash-out treatment

This wash-out serum is jam-packed with hair-healthy, fatty-acid-rich oils: meadowfoam seed oil, chia seed oil, aai fruit oil, and rapeseed oil, to name a select few. It's best used as a pre-shampoo product; those heavyweight oils might weigh down the strands (unless you're gunning for a chic, slicked-back look; then by all means, marinate away). But if your strands are especially thirsty, it can also work as an overnight mask.

Considerations: Vegan, Cruelty-free, Leave-in treatment, Lightweight

This leave-in tonic is beloved for plumping the hair fibers and increasing volume, so you can rock a thick, full-bodied 'do. It contains a "hair energy complex" to improve the density of the hair shaft, along with mung bean and clover extracts to soothe and protect the scalp.

Considerations: Vegan, Cruelty-free, Leave-in treatment, Lightweight

Scalp buildup can hinder your hair growth goals, which is why this daily serum includes apple cider vinegar to exfoliate and unclog hair follicles. Aside from the star ingredient, you'll find peptides to stimulate collagen production, organic maca root for antioxidant properties, hyaluronic acid and aloe vera for hydration, and lavender extract to further stimulate the scalp. Not to mention, the formula is super lightweight and absorbs almost instantly.

Other ways to encourage hair growth.

As you can tell by now, hair growth is a complex topic that may require multiple angles. So in addition to snagging one of the serums above, you might fare well with these extra methods:

1.Scalp massages

"Beautiful, strong hair depends on good blood circulation, proper nutrition, and a healthy and supple scalp," says board-certified dermatologist Raechele Cochran Gathers, M.D., hair care expert and founder of MDHairMixtress, about scalp massages. In fact, regular massages have been clinically shown to promote hair growth. That's because they help release tension and encourage blood flow to the areawhich, in turn, delivers oxygen and hair-healthy nutrients to the follicles.

While you can always give yourself a tension-relieving scalp massage with nothing but your fingertips, a scalp massager tool can help you address those hard-to-reach places, like the very back of the head or behind the ears. This Brush From Hairstory is a solid option to use in and out of the shower, or find mbg's full list of favorite scalp massagers here.

2.Collagen & biotin supplements

Ready for a little hair anatomy lesson? Hair is made of the protein keratin, which has an amino acid profile including cysteine, serine, glutamic acid, glycine, and proline. Both collagen and biotin supplements have high amounts of many of these amino acids, meaning the supplements provide the body with the building blocks of hair.* Research backs this up, too, as studies show taking these supplements can support hair growth.*

Check out our list of collagen and biotin supplements, or if you're looking for a one-stop shop that has 'em both, go ahead and grab mbg's beauty & gut collagen+. In addition to 17.7 grams of grass-fed collagen peptides and 500 micrograms of biotin, it has vitamins C and E for enhanced collagen production and antioxidant support, hyaluronic acid for skin hydration, and curcumin from turmeric extract and sulforaphane from broccoli seed extract for supporting detoxification and combating oxidative stress.*

3.Clarifying scrubs

Too much scalp buildup can suffocate the follicle root, which is literally the source of hair growth. That's why many experts tout scalp-stimulating treatments for speedier hair growth; a clean, happy scalp leads to full, lush strands.

If you think you might be dealing with buildup, try folding a scalp scrub into your routine. With these, you can choose physical exfoliators, with granules (like sugar and salt) to manually remove buildup, or chemical formulas, with naturally exfoliating acids and enzymes to dissolve dead skin and lift up debris.

mbg review process.

At mbg, high standards are earned and there are no shortcuts. Our beauty editors stay up to date on the latest ingredient research and innovation. It's a dynamic, continuously evolving space, and it's important we look into the science so we can make informed choices about which formulas earn our stamp of approval (figuratively speaking).

Our high standards also come from testing productsmany, many products. Our editors and writers rigorously test and research the products featured in our roundups to offer you the best, most informed recommendations. When we write reviews, you can trust we spend quality time with the formulas: We don't simply rave about products we've slathered on the back of our hand. We endorse products we've tried and loved.

Learn more about our testing process and clean beauty standards here.

The takeaway.

Even if hair growth isn't your main concern right now, these serums can all help moisturize and nurture the scalpwhich anyone can benefit from, no matter your length goals. Again, helping your hair grow faster is a tricky feat; make sure to keep all of these tips in mind before embarking on your hair growth journey.

If you are pregnant, breastfeeding, or taking medications, consult with your doctor before starting a supplement routine. It is always optimal to consult with a health care provider when considering what supplements are right for you.

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What’s Your Biological Age? A New ‘Aging Clock’ Has the Answer – Singularity Hub

By daniellenierenberg

How old are you, really?

It seems like a simple question. Its based on when youre born. Yet we all know people who seem much younger than their chronological age. They have radiant skin and hair. They seem sharper than their age would suggest. Theyre highly active with astonishing energy.

Why? Studies have repeatedly shown that cells, tissues, and people have a biological age that may or may not correspond to how old they are in terms of birthdays. Longevity scientists have taken note. As they look into what makes us age, one main metric pops up: a biological aging clocka measure that reflects your bodys age irrespective of your years on Earth.

One of the most popular aging clocks dives deep into our cells. As we age, our genomes add on chunks of chemicals that alter their gene expression. These markers, dubbed epigenetic modifications, normally just tack on and off like Velcro. But with age, certain bits of the genome add far more chunks, which essentially work to shut the genes off.

In other words, our cells have an epigenetic age (EpiAge). But what, if anything, does the clock mean for longevity?

Dr. Steve Horvath had his eye on extending lifespan ever since he was a teenager. A biomathematician, he set his eyes on using computation modeling and AI to understand how to extend life.

But to find the key, he needed a focus. Horvaths idea stemmed from epigeneticsa powerful way our bodies control DNA expression without altering the DNA strands themselves. Epigenetics is an extremely fluid dance, with multiple chemical components latching onto or falling off of DNA strands. The epigenetic dance changes with age, though some changes seem consistent across time. This led Horvath to ask: can we use these epigenetic markers to gauge a cells age?

Apparently, the answer is yes. After gathering and analyzing over 13,000 human samples, Horvath found an impressive measuring tape for aging. The key was a type of epigenetic modification called methylation, which tends to rest on DNA spots dubbed CpG islands. (We all need a summer break!)

His team developed an algorithm for biological agea cellular biological clockthat impressed longevity researchers with its accuracy throughout the body. Rather than a one-off, EpiAge seems to work for multiple organs and tissues, potentially shining light on how aging happens.

I wanted to develop a method that would work in many or most tissues. It was a very risky project, Horvath said at the time.

The clocks median error was a measly 3.6 years, meaning that it could gauge a persons age within 43 months. Even more impressive, the clock used a simple statistical model, which looked at a certain type of epigenetic modificationDNA methylationat just two target sites on DNA. All it took was a saliva sample. With more work, Horvath found even more patterns that reflected the age of certain types of cells, such as neurons and blood cells. The test was amazingly good, said Kevin Bryant at Zymo Research, a biotechnology company in Irvine, California at the time.

EpiAge also began looking under the veil. The discrepancy between epigenetic age as estimated by these clocks, and chronological age is referred to as EpiAge acceleration, the authors said. Epidemiological studies have linked EpiAge acceleration to a wide variety of pathologies, health states, lifestyle, mental state, and environmental factors, indicating that epigenetic clocks tap into critical biological processes that are involved in aging.

Yet one glaring question remained: what exactly is the EpiAge clock measuring?

If youre having trouble linking epigenetic modifications to aging, I feel ya. How and why do what are essentially fridge magnets for the genome change anything?

Let me introduce you to the wheel of aging.

Zooming in on our genes, the genome becomes more unstablemeaning that theres more chances for mutations. Telomeres, the protective cap on the genes, waste away. Proteins start behaving wonkily, sometimes forming into clumps that clog up the cells waste disposal system, potentially leading to Alzheimers and other neurodegenerative disorders. The cells energy factory, the mitochondria, sputters and malfunctions. Cells can no longer sense nutrients floating around. Even worse, some cells give up completely and turn into senescent zombie cellsthey dont die, but dont perform normal functions, instead spewing out toxic immune chemicals.

The thing is, we dont know why these different types of aging behaviors happen. And when measuring age, we dont know how aging clocks correspond to these hallmarks. Its partly why there are multiple aging clocks. EpiAge is one. Another is (not kidding) Skin & blood, which predicts lifespan and relates to many age-related conditions.

In a new study, published in Nature Aging, Horvath and Dr. Ken Raj at Altos Labs took a first step at linking the epigenetic clock to the hallmarks of aging. Using donated human cells from 14 healthy peoplegrown inside containers in the labthe team split the cells into four groups. One was zapped with radiation, another tweaked to become cancerous, and a third that turned into zombie senescent cells. The fourth group was left alone without any treatment.

These treatments reflect major hallmarks of aging, the authors explained. Radiation in small doses, for example, destabilizes the genome that mimics aging, and the cells became senescent is just two weeks. Cancer-like cells also aged heavily in just a few days. Yet surprisingly, the cells didnt age according to EpiAge, even when tested in other cells. These results, obtained through investigation using different primary human and mouse cells and multiple radiation doses and regimens, demonstrate that epigenetic agingis not affected by genomic instability induced by radiation-induced DNA breaks, the authors said.

In other words, what EpiAge measureschanges to a cells CpG epigenomedoesnt necessarily predict a cells zombie senescence status. Similarly, the clock didnt seem to match up with telomere problems or general genome stability.

What did match up? Energy. Breaking it down, EpiAge is associated with a cells ability to sense nutrientsa key signal that tells it to grow, reproduce, or shrivel. Another associate is mitochondria activity, which generates power for the cell. Finally, EpiAge also seems to reflect the amount of stem cells in the samples, which changes starting early.

The observation that aging begins so early in life is possible because age can now be measured based on the biology of the cell instead of the passing of time, the authors said. For aging clocks, this measurement allows interrogation of the link between age and longevity.

While aging clocks are increasingly becoming mainstream, the question is what exactly each measures. The excitement following the development of epigenetic clocks has been tinged with uncertainty as to the meaning of their measurements.

This study is one of the first to link a powerful aging clock to the hallmarks of aging. The connection of epigenetic aging to four of the hallmarks of aging implies that these hallmarks are also mutually connected at deeper levels, the authors wrote.

In other words, weve started peeking into what unites the multiple veins of aging. The absence of a connection between the other aging hallmarks and epigenetic aging suggests that aging is a consequence of multiparallel mechanisms, the authors said. Some may be because of epigenetic changes; others simply due to wear and tear. Bring on the aging multiverse of madness.

Image Credit:Icons8_team from Pixabay

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Scientists Rejuvenate Skin Cells by 30 Years, with Pioneering Potential – BioSpace

By daniellenierenberg

As previously reported by BioSpace, a group of scientists from The Babraham Institutein the United Kingdom was able to successfully rejuvenate skin cells by a full 30 years.

The research team published a study in eLife Sciences last month describing their process of using induced pluripotent stem cell (iPSC) reprogramming to reverse aging effects at the cellular level.

Study co-author Ins Milagre told BioSpace that the research process was a team effort. In Lead Author Wolf Reiks lab, she was working on cell reprogramming while a colleague focused on the epigenetic clock.

Milagre came into her research career driven by an early interest in biology. I was fascinated by biology all of my life. I had a very good biology teacher when I was in high school, she said.

She explained that she was also a huge fan of the drama series The X-Files, seeing Gillian Anderson's character, Dana Scully, as a role model. I thought that being a scientist must be very cool. This combination made me decide to go into biology.

The research teams original hypothesis came from knowing that we can easily program cells to be zero years of age. No matter what age they are in the beginning, the cells normally reprogram back to embryonic age, or zero years of age.

Though reprogrammed embryonic cells are free of gradual aging decline, they lack identity and thus function. The research team began to consider what would happen if they could get the cells to only partially rejuvenate.

With embryonic cells, downstream applications can be a problem. We thought that maybe we could just rejuvenate the cells and then coax them back into being the cell of origin, Milagre explained. At first, the idea was casually discussed over happy hour, but then the team found that preliminary experiments yielded promising results.

They utilized Yamanaka factors (Oct4, Sox2, Klf4, c-Myc), which are typically used to differentiate cells into the embryonic stem cell stage. Instead of allowing the full time that it takes for cells to get to the embryonic life stage, we decided to stop the reprogramming process halfway through, Milagre said.

By doing this, we were able to get the cells to a younger age. They were easily reverted back to the original cell type, which in our case, were skin cells. Pausing the process in the middle allowed the cells to become a younger version of the same cell type. The researchers named the novel method maturation phase transient reprogramming (MPTR).

What I find very exciting about this study is that we showed that it's possible to rejuvenate cells, she said. Though the Yamanaka factors have been used in other labs, the Babraham Institute team was the first to rejuvenate cells by a full 30 years.

Courtesy of the Babraham Institute

The scientists observed several benefits of the functionally younger cells. The skin cells were better able to produce collagen, and they were responding better to wound healing sites, Milagre said. The above photo depicts the collagen levels of the skin cells before and after rejuvenation. On the left are the original 53-year-old skin cells, and on the right are the reprogrammed cells. The collagen levels are depicted in red.

Milagre noted that the study is very preliminary, with much more research to be completed before the technology is safe and available. We only tested this in skin cells, so we don't know if this is also possible in other cell types, though we believe that it probably is based on similar work from other groups.

Another element that must be studied is how the technology will work without using the same viral vectors. We need to make a safer technology to do this. As a proof of principle, we showed that it's possible to rejuvenate cells by 30 years. Now, we need to do more research to be able to eventually move this technology into a more clinical setting.

Once the technology is safe and ready, Milagre noted that many downstream applications could be possible. We can think about trying to tackle neurodegenerative and degenerative disorders as well as ameliorating some aging effects. If we can get cells to be functionally younger, even if we don't expand peoples lives, we might be able to give people a better quality of life.

Reik explained in an earlier article that the findings could eventually lead to targeting specific genes that would be able to rejuvenate without any reprogramming. Milagre said that Yamanaka factors are working as pioneers that can start new gene expression programs. If we understand which genes are being activated downstream, we can eventually think about modulating these genes. We can try switching on a minimum number of effector genes. This would be a way to overcome using viral vectors.

Though potential future benefits of the findings are a long way off, the team is still considering the people they may help down the line. We hope the technology will help people live better lives without diseases, or without the consequences of a disease even if they still have it, Milagre said.

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Lasers, Fish-Skin Bandages and Pain-Free Vaccines: The Winners of Our 3rd Annual STEM Writing Contest – The New York Times

By daniellenierenberg

Saahil Joshi, age 17, Crystal Springs Uplands School, Hillsborough, Calif.: Too Many Cooks Spoil the Broth: The Science and Future of Drug-Drug Interactions

Micah: Salt: The Sapid and Sophisticated Seasoning

Katherine Kricorian, age 17, Santa Susana High School, Simi Valley, Calif.: From Algae to Energy: A Blooming Solution to Pollution

Chloe Lee, age 14, Korea International School Pangyo Campus, Gyeonggi-do, Korea: Do Plants Have Feelings?

Seungjae (Andy) Lee, age 13, Hong Kong International School, Tai Tam, Hong Kong: Keeping Your Pet Friend Forever: Is Cloning a Soul Possible?

Zhuocheng Li, age 16, Green Hope High School, Cary, N.C.: The Blood That Saved Countless Lives

Andrew C. Lin, age 12, Visions in Education Homeschool Academy, Carmichael, Calif.: Breaking the Speech Barrier

Andy Lu, age 16, Desert Vista High School, Phoenix: Hypersonic Flight: Can We Go Faster?

Camille: Sugar and the Body: A Bittersweet Relationship

Natalia Meza, age 17, American School of Madrid, Madrid: What Happens in Vagus, Stays in Vagus?

Aman Mistry, age 17, Smithtown High School, East Saint James, N.Y.: Helping a Blind Man See: The Miracle of Optogenetics

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Have you heard of the goodness of Swiss apple stem cells? – Times of India

By daniellenierenberg

We all love trying out new skincare products that give our skin that supple plump and glow. Many of us also use anti-ageing and skin firming products to help reduce those stubborn wrinkles, pigmentation and fine lines. Ever heard the saying, An apple a day, keeps the doctor away? Now, what if we told you that this apple can help your skin without you actually having to eat it? Got you wondering how now, did we?Until several years ago, the tart, unappealing variant of the Swiss-grown Uttwiler Sptlauber apples, wasnt proving to add any value in terms of offering. This was until some scientists discovered the unusual longevity of the stem cells that kept these apples alive months after other apples shriveled and fell off their trees. What are stem cells, you ask? Stem cells are extremely unique in a way that they have the ability to go through numerous cycles and cell divisions while maintaining the undifferentiated state. Essentially, stem cells are capable of self-renewal and can transform themselves into other cell types of the same tissue. One of their primary roles is to replenish dying cells and regenerate damaged tissue. Stem cells provide the ability for species to renew and repair themselves. Plants are rooted in the ground and have to survive extreme weather changes, therefore their stem cells contain much stronger antioxidant contents than those of humans cells.

But how does this help your skin? Heres a list of the goodness that Swiss apple stem cells can have on your skin.

The high antioxidant found in plant stem cells supports the skin in combating free radicals that would otherwise cause skin damage. They give your skin the tools to protect itself, offering immense anti-ageing and anti-inflammatory benefits. The boost of antioxidants and amino acids helps boost collagen production and keeps your skin radiant and youthful.

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Why haven’t we cloned a human yet? – Livescience.com

By daniellenierenberg

In 1996, Dolly the sheep made headlines around the world after becoming the first mammal to be successfully cloned from an adult cell. Many commentators thought this would catalyze a golden age of cloning, with numerous voices speculating that the first human clone must surely be just a few years away.

Some people suggested that human clones could play a role in eradicating genetic diseases, while others considered that the cloning process could, eventually, eliminate birth defects (despite research by a group of French scientists in 1999 finding that cloning may actually increase the risk of birth defects).

There have been various claims all unfounded, it is important to add of successful human cloning progams since the success of Dolly. In 2002, Brigitte Boisselier, a French chemist and devout supporter of Ralism a UFO religion based on the idea that aliens created humanity claimed that she and a team of scientists had successfully delivered the first cloned human, whom she named Eve.

However, Boisselier was unwilling or indeed unable to provide any evidence, and so it is widely believed to be a hoax.

So why, almost 30 years on from Dolly, haven't humans been cloned yet? Is it primarily for ethical reasons, are there technological barriers, or is it simply not worth doing?

Related: What are the alternatives to animal testing?

"Cloning" is a broad term, given it can be used to describe a range of processes and approaches, but the aim is always to produce "genetically identical copies of a biological entity," according to the National Human Genome Research Institute (NHGRI).

Any attempted human cloning would most likely utilize "reproductive cloning" techniques an approach in which a "mature somatic cell," most probably a skin cell, would be used, according to NHGRI. The DNA extracted from this cell would be placed into the egg cell of a donor that has "had its own DNA-containing nucleus removed."

The egg would then begin to develop in a test tube before being "implanted into the womb of an adult female," according to NHGRI.

However, while scientists have cloned many mammals, including cattle, goats, rabbits and cats, humans have not made the list.

"I think there is no good reason to make [human] clones," Hank Greely, a professor of law and genetics at Stanford University who specializes in ethical, legal and social issues arising from advances in the biosciences, told Live Science in an email.

"Human cloning is a particularly dramatic action, and was one of the topics that helped launch American bioethics," Greely added.

The ethical concerns around human cloning are many and varied. According to Britannica, the potential issues encompass "psychological, social and physiological risks." These include the idea that cloning could lead to a "very high likelihood" of loss of life, as well as concerns around cloning being used by supporters of eugenics. Furthermore, according to Britannica, cloning could be deemed to violate "principles of human dignity, freedom and equality."

In addition, the cloning of mammals has historically resulted in extremely high rates of death and developmental abnormalities in the clones, Live Science previously reported.

Another core issue with human cloning is that, rather than creating a carbon copy of the original person, it would produce an individual with their own thoughts and opinions.

"We've all known clones identical twins are clones of each other and thus we all know that clones aren't the same person," Greely explained.

A human clone, Greely continued, would only have the same genetic makeup as someone else they would not share other things such as personality, morals or sense of humor: these would be unique to both parties.

People are, as we well know, far more than simply a product of their DNA. While it is possible to reproduce genetic material, it is not possible to exactly replicate living environments, create an identical upbringing, or have two people encounter the same life experiences.

So, if scientists were to clone a human, would there be any benefits, scientific or otherwise?

"There are none that we should be willing to consider," Greely said, emphasizing that the ethical concerns would be impossible to overlook.

However, if moral considerations were removed entirely from the equation, then "one theoretical benefit would be to create genetically identical humans for research purposes," Greely said, though he was keen to reaffirm his view that this should be thought of as "an ethical non-starter."

Greely also stated that, regardless of his own personal opinion, some of the potential benefits associated with cloning humans have, to a certain degree, been made redundant by other scientific developments.

"The idea of using cloned embryos for purposes other than making babies, for example producing human embryonic stem cells identical to a donor's cells, was widely discussed in the early 2000s," he said, but this line of research became irrelevant and has subsequently not been expanded upon post-2006, the year so-called induced pluripotent stem cells (iPSCs) were discovered. These are "adult" cells that have been reprogrammed to resemble cells in early development.

Shinya Yamanaka, a Japanese stem cell researcher and 2012 Nobel Prize winner, made the discovery when he "worked out how to return adult mouse cells to an embryonic-like state using just four genetic factors," according to an article in Nature. The following year, Yamanaka, alongside renowned American biologist James Thompson, managed to do the same with human cells.

When iPSCs are "reprogrammed back into an embryonic-like pluripotent state," they enable the "development of an unlimited source of any type of human cell needed for therapeutic purposes," according to the Center of Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles.

Therefore, instead of using embryos, "we can effectively do the same thing with skin cells," Greely said.

This development in iPSC technology essentially rendered the concept of using cloned embryos both unnecessary and scientifically inferior.

Related: What is the most genetically diverse species?

Nowadays, iPSCs can be used for research in disease modeling, medicinal drug discovery and regenerative medicine, according to a 2015 paper published in the journal Frontiers in Cell and Developmental Biology.

Additionally, Greely also suggested that human cloning may simply no longer be a "sexy" area of scientific study, which could also explain why it has seen very little development in recent years.

He pointed out that human germline genome editing is now a more interesting topic in the public's mind, with many curious about the concept of creating "super babies," for example. Germline editing, or germline engineering, is a process, or series of processes, that create permanent changes to an individuals genome. These alterations, when introduced effectively, become heritable, meaning they will be handed down from parent to child.

Such editing is controversial and yet to be fully understood. In 2018, the Council of Europe Committee on Bioethics, which represents 47 European states, released a statement saying that "ethics and human rights must guide any use of genome editing technologies in human beings," adding that "the application of genome editing technologies to human embryos raises many ethical, social and safety issues, particularly from any modification of the human genome which could be passed on to future generations."

However, the council also noted that there is "strong support" for using such engineering and editing technologies to better understand "the causes of diseases and their future treatment," noting that they offer "considerable potential for research in this field and to improve human health."

George Church, a geneticist and molecular engineer at Harvard University, supports Greely's assertion that germline editing is likely to garner more scientific interest in the future, especially when compared with "conventional" cloning.

"Cloning-based germline editing is typically more precise, can involve more genes, and has more efficient delivery to all cells than somatic genome editing," he told Live Science.

However, Church was keen to urge caution, and admitted that such editing has not yet been mastered.

"Potential drawbacks to address include safety, efficacy and equitable access for all," he concluded.

Originally published on Live Science.

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